[{"article_type":"original","page":"P629-644.E8","publication":"Neuron","citation":{"ama":"Takeo YH, Shuster SA, Jiang L, et al. GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. Neuron. 2021;109(4):P629-644.E8. doi:10.1016/j.neuron.2020.11.028","ista":"Takeo YH, Shuster SA, Jiang L, Hu M, Luginbuhl DJ, Rülicke T, Contreras X, Hippenmeyer S, Wagner MJ, Ganguli S, Luo L. 2021. GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. Neuron. 109(4), P629–644.E8.","ieee":"Y. H. Takeo et al., “GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells,” Neuron, vol. 109, no. 4. Elsevier, p. P629–644.E8, 2021.","apa":"Takeo, Y. H., Shuster, S. A., Jiang, L., Hu, M., Luginbuhl, D. J., Rülicke, T., … Luo, L. (2021). GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.11.028","mla":"Takeo, Yukari H., et al. “GluD2- and Cbln1-Mediated Competitive Synaptogenesis Shapes the Dendritic Arbors of Cerebellar Purkinje Cells.” Neuron, vol. 109, no. 4, Elsevier, 2021, p. P629–644.E8, doi:10.1016/j.neuron.2020.11.028.","short":"Y.H. Takeo, S.A. Shuster, L. Jiang, M. Hu, D.J. Luginbuhl, T. Rülicke, X. Contreras, S. Hippenmeyer, M.J. Wagner, S. Ganguli, L. Luo, Neuron 109 (2021) P629–644.E8.","chicago":"Takeo, Yukari H., S. Andrew Shuster, Linnie Jiang, Miley Hu, David J. Luginbuhl, Thomas Rülicke, Ximena Contreras, et al. “GluD2- and Cbln1-Mediated Competitive Synaptogenesis Shapes the Dendritic Arbors of Cerebellar Purkinje Cells.” Neuron. Elsevier, 2021. https://doi.org/10.1016/j.neuron.2020.11.028."},"date_published":"2021-02-17T00:00:00Z","scopus_import":"1","day":"17","article_processing_charge":"No","title":"GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells","status":"public","intvolume":" 109","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"8544","oa_version":"Preprint","type":"journal_article","abstract":[{"lang":"eng","text":"The synaptotrophic hypothesis posits that synapse formation stabilizes dendritic branches, yet this hypothesis has not been causally tested in vivo in the mammalian brain. Presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2 mediate synaptogenesis between granule cells and Purkinje cells in the molecular layer of the cerebellar cortex. Here we show that sparse but not global knockout of GluD2 causes under-elaboration of Purkinje cell dendrites in the deep molecular layer and overelaboration in the superficial molecular layer. Developmental, overexpression, structure-function, and genetic epistasis analyses indicate that dendrite morphogenesis defects result from competitive synaptogenesis in a Cbln1/GluD2-dependent manner. A generative model of dendritic growth based on competitive synaptogenesis largely recapitulates GluD2 sparse and global knockout phenotypes. Our results support the synaptotrophic hypothesis at initial stages of dendrite development, suggest a second mode in which cumulative synapse formation inhibits further dendrite growth, and highlight the importance of competition in dendrite morphogenesis."}],"issue":"4","quality_controlled":"1","project":[{"_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.06.14.151258"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.neuron.2020.11.028","month":"02","publication_identifier":{"eissn":["1097-4199"]},"publication_status":"published","publisher":"Elsevier","department":[{"_id":"SiHi"}],"acknowledgement":"We thank M. Mishina for GluD2fl frozen embryos, T.C. Südhof and J.I. Morgan for Cbln1fl mice, L. Anderson for help in generating the MADM alleles, W. Joo for a previously unpublished construct, M. Yuzaki, K. Shen, J. Ding, and members of the Luo lab, including J.M. Kebschull, H. Li, J. Li, T. Li, C.M. McLaughlin, D. Pederick, J. Ren, D.C. Wang and C. Xu for discussions and critiques of the manuscript, and M. Yuzaki for supporting Y.H.T. during the final phase of this project. Y.H.T. was supported by a JSPS fellowship; S.A.S. was supported by a Stanford Graduate Fellowship and an NSF Predoctoral Fellowship; L.J. is supported by a Stanford Graduate Fellowship and an NSF Predoctoral Fellowship; M.J.W. is supported by a Burroughs Wellcome Fund CASI Award. This work was supported by an NIH grant (R01-NS050538) to L.L.; the European Research Council (ERC) under the European Union's Horizon 2020 research and innovations programme (No. 725780 LinPro) to S.H.; and Simons and James S. McDonnell Foundations and an NSF CAREER award to S.G.; L.L. is an HHMI investigator.","year":"2021","date_updated":"2024-03-06T12:12:48Z","date_created":"2020-09-21T11:59:47Z","volume":109,"author":[{"full_name":"Takeo, Yukari H.","last_name":"Takeo","first_name":"Yukari H."},{"full_name":"Shuster, S. Andrew","last_name":"Shuster","first_name":"S. Andrew"},{"full_name":"Jiang, Linnie","last_name":"Jiang","first_name":"Linnie"},{"full_name":"Hu, Miley","last_name":"Hu","first_name":"Miley"},{"full_name":"Luginbuhl, David J.","last_name":"Luginbuhl","first_name":"David J."},{"full_name":"Rülicke, Thomas","last_name":"Rülicke","first_name":"Thomas"},{"full_name":"Contreras, Ximena","last_name":"Contreras","first_name":"Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer"},{"last_name":"Wagner","first_name":"Mark J.","full_name":"Wagner, Mark J."},{"full_name":"Ganguli, Surya","first_name":"Surya","last_name":"Ganguli"},{"last_name":"Luo","first_name":"Liqun","full_name":"Luo, Liqun"}],"ec_funded":1},{"citation":{"ama":"Hansen AH. Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration. 2021. doi:10.15479/at:ista:9962","ista":"Hansen AH. 2021. Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration. Institute of Science and Technology Austria.","apa":"Hansen, A. H. (2021). Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:9962","ieee":"A. H. Hansen, “Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration,” Institute of Science and Technology Austria, 2021.","mla":"Hansen, Andi H. Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration. Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:9962.","short":"A.H. Hansen, Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration, Institute of Science and Technology Austria, 2021.","chicago":"Hansen, Andi H. “Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects in Radial Projection Neuron Migration.” Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:9962."},"page":"182","date_published":"2021-09-02T00:00:00Z","keyword":["Neuronal migration","Non-cell-autonomous","Cell-autonomous","Neurodevelopmental disease"],"has_accepted_license":"1","article_processing_charge":"No","day":"02","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"9962","ddc":["570"],"title":"Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration","status":"public","oa_version":"Published Version","file":[{"file_size":10629190,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"ahansen","access_level":"closed","embargo_to":"open_access","file_name":"Thesis_Hansen.docx","checksum":"66b56f5b988b233dc66a4f4b4fb2cdfe","date_updated":"2022-09-03T22:30:04Z","date_created":"2021-08-30T09:17:39Z","relation":"source_file","file_id":"9971"},{"content_type":"application/pdf","file_size":13457469,"creator":"ahansen","file_name":"Thesis_Hansen_PDFA-1a.pdf","access_level":"open_access","date_created":"2021-08-30T09:29:44Z","date_updated":"2022-09-03T22:30:04Z","checksum":"204fa40321a1c6289b68c473634c4bf3","relation":"main_file","embargo":"2022-09-02","file_id":"9972"}],"type":"dissertation","alternative_title":["ISTA Thesis"],"abstract":[{"lang":"eng","text":"The brain is one of the largest and most complex organs and it is composed of billions of neurons that communicate together enabling e.g. consciousness. The cerebral cortex is the largest site of neural integration in the central nervous system. Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final position, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating radial neuronal migration in vivo are however still unclear. Recent evidence suggests that distinct signaling cues act cell-autonomously but differentially at certain steps during the overall migration process. Moreover, functional analysis of genetic mosaics (mutant neurons present in wild-type/heterozygote environment) using the MADM (Mosaic Analysis with Double Markers) analyses in comparison to global knockout also indicate a significant degree of non-cell-autonomous and/or community effects in the control of cortical neuron migration. The interactions of cell-intrinsic (cell-autonomous) and cell-extrinsic (non-cell-autonomous) components are largely unknown. In part of this thesis work we established a MADM-based experimental strategy for the quantitative analysis of cell-autonomous gene function versus non-cell-autonomous and/or community effects. The direct comparison of mutant neurons from the genetic mosaic (cell-autonomous) to mutant neurons in the conditional and/or global knockout (cell-autonomous + non-cell-autonomous) allows to quantitatively analyze non-cell-autonomous effects. Such analysis enable the high-resolution analysis of projection neuron migration dynamics in distinct environments with concomitant isolation of genomic and proteomic profiles. Using these experimental paradigms and in combination with computational modeling we show and characterize the nature of non-cell-autonomous effects to coordinate radial neuron migration. Furthermore, this thesis discusses recent developments in neurodevelopment with focus on neuronal polarization and non-cell-autonomous mechanisms in neuronal migration."}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"project":[{"name":"Molecular Mechanisms of Radial Neuronal Migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812"}],"doi":"10.15479/at:ista:9962","language":[{"iso":"eng"}],"degree_awarded":"PhD","supervisor":[{"orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","first_name":"Simon","full_name":"Hippenmeyer, Simon"}],"publication_identifier":{"issn":["2663-337X"]},"month":"09","year":"2021","publisher":"Institute of Science and Technology Austria","department":[{"_id":"GradSch"},{"_id":"SiHi"}],"publication_status":"published","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"8569"},{"relation":"part_of_dissertation","status":"public","id":"960"}]},"author":[{"full_name":"Hansen, Andi H","first_name":"Andi H","last_name":"Hansen","id":"38853E16-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-09-22T09:58:30Z","date_created":"2021-08-29T12:36:50Z","file_date_updated":"2022-09-03T22:30:04Z","license":"https://creativecommons.org/licenses/by/4.0/"},{"publication_status":"published","department":[{"_id":"SiHi"}],"publisher":"Frontiers Media","year":"2020","date_updated":"2021-01-12T08:15:42Z","date_created":"2020-05-11T08:18:48Z","volume":5,"author":[{"full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","last_name":"Beattie","first_name":"Robert J"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer"},{"last_name":"Pauler","first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian"}],"article_number":"48","file_date_updated":"2020-07-14T12:48:03Z","ec_funded":1,"quality_controlled":"1","project":[{"grant_number":"M02416","_id":"264E56E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex"},{"grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"language":[{"iso":"eng"}],"doi":"10.3389/feduc.2020.00048","month":"05","publication_identifier":{"issn":["2504-284X"]},"status":"public","title":"SCOPES: Sparking curiosity through Open-Source platforms in education and science","ddc":["570"],"intvolume":" 5","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"7814","file":[{"date_updated":"2020-07-14T12:48:03Z","date_created":"2020-05-11T11:34:08Z","checksum":"a24ec24e38d843341ae620ec76c53688","relation":"main_file","file_id":"7818","file_size":1402146,"content_type":"application/pdf","creator":"dernst","file_name":"2020_FrontiersEduc_Beattie.pdf","access_level":"open_access"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"text":"Scientific research is to date largely restricted to wealthy laboratories in developed nations due to the necessity of complex and expensive equipment. This inequality limits the capacity of science to be used as a diplomatic channel. Maker movements use open-source technologies including additive manufacturing (3D printing) and laser cutting, together with low-cost computers for developing novel products. This movement is setting the groundwork for a revolution, allowing scientific equipment to be sourced at a fraction of the cost and has the potential to increase the availability of equipment for scientists around the world. Science education is increasingly recognized as another channel for science diplomacy. In this perspective, we introduce the idea that the Maker movement and open-source technologies have the potential to revolutionize science, technology, engineering and mathematics (STEM) education worldwide. We present an open-source STEM didactic tool called SCOPES (Sparking Curiosity through Open-source Platforms in Education and Science). SCOPES is self-contained, independent of local resources, and cost-effective. SCOPES can be adapted to communicate complex subjects from genetics to neurobiology, perform real-world biological experiments and explore digitized scientific samples. We envision such platforms will enhance science diplomacy by providing a means for scientists to share their findings with classrooms and for educators to incorporate didactic concepts into STEM lessons. By providing students the opportunity to design, perform, and share scientific experiments, students also experience firsthand the benefits of a multinational scientific community. We provide instructions on how to build and use SCOPES on our webpage: http://scopeseducation.org.","lang":"eng"}],"article_type":"original","publication":"Frontiers in Education","citation":{"ama":"Beattie RJ, Hippenmeyer S, Pauler F. SCOPES: Sparking curiosity through Open-Source platforms in education and science. Frontiers in Education. 2020;5. doi:10.3389/feduc.2020.00048","ista":"Beattie RJ, Hippenmeyer S, Pauler F. 2020. SCOPES: Sparking curiosity through Open-Source platforms in education and science. Frontiers in Education. 5, 48.","apa":"Beattie, R. J., Hippenmeyer, S., & Pauler, F. (2020). SCOPES: Sparking curiosity through Open-Source platforms in education and science. Frontiers in Education. Frontiers Media. https://doi.org/10.3389/feduc.2020.00048","ieee":"R. J. Beattie, S. Hippenmeyer, and F. Pauler, “SCOPES: Sparking curiosity through Open-Source platforms in education and science,” Frontiers in Education, vol. 5. Frontiers Media, 2020.","mla":"Beattie, Robert J., et al. “SCOPES: Sparking Curiosity through Open-Source Platforms in Education and Science.” Frontiers in Education, vol. 5, 48, Frontiers Media, 2020, doi:10.3389/feduc.2020.00048.","short":"R.J. Beattie, S. Hippenmeyer, F. Pauler, Frontiers in Education 5 (2020).","chicago":"Beattie, Robert J, Simon Hippenmeyer, and Florian Pauler. “SCOPES: Sparking Curiosity through Open-Source Platforms in Education and Science.” Frontiers in Education. Frontiers Media, 2020. https://doi.org/10.3389/feduc.2020.00048."},"date_published":"2020-05-08T00:00:00Z","day":"08","article_processing_charge":"No","has_accepted_license":"1"},{"ec_funded":1,"abstract":[{"text":"The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we reported that a substantial proportion of blood vessels in the adult brain sporadically occluded and regressed. Their regression proceeded through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels were found to be widespread in mouse, monkey and human brains. Both brief occlusions of the middle cerebral artery and lipopolysaccharide-mediated inflammation induced an increase of vessel regression. Blockage of leukocyte adhesion to endothelial cells alleviated LPS-induced vessel regression. We further revealed that blood vessel regression caused a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and glutamate production. Our results elucidate the mechanism of vessel regression and its role in neuronal function in the adult brain.","lang":"eng"}],"type":"preprint","author":[{"last_name":"Gao","first_name":"Xiaofei","full_name":"Gao, Xiaofei"},{"full_name":"Li, Jun-Liszt","first_name":"Jun-Liszt","last_name":"Li"},{"full_name":"Chen, Xingjun","last_name":"Chen","first_name":"Xingjun"},{"first_name":"Bo","last_name":"Ci","full_name":"Ci, Bo"},{"first_name":"Fei","last_name":"Chen","full_name":"Chen, Fei"},{"full_name":"Lu, Nannan","first_name":"Nannan","last_name":"Lu"},{"full_name":"Shen, Bo","first_name":"Bo","last_name":"Shen"},{"full_name":"Zheng, Lijun","last_name":"Zheng","first_name":"Lijun"},{"full_name":"Jia, Jie-Min","last_name":"Jia","first_name":"Jie-Min"},{"full_name":"Yi, Yating","last_name":"Yi","first_name":"Yating"},{"last_name":"Zhang","first_name":"Shiwen","full_name":"Zhang, Shiwen"},{"first_name":"Ying-Chao","last_name":"Shi","full_name":"Shi, Ying-Chao"},{"last_name":"Shi","first_name":"Kaibin","full_name":"Shi, Kaibin"},{"full_name":"Propson, Nicholas E","last_name":"Propson","first_name":"Nicholas E"},{"full_name":"Huang, Yubin","last_name":"Huang","first_name":"Yubin"},{"full_name":"Poinsatte, Katherine","first_name":"Katherine","last_name":"Poinsatte"},{"full_name":"Zhang, Zhaohuan","first_name":"Zhaohuan","last_name":"Zhang"},{"last_name":"Yue","first_name":"Yuanlei","full_name":"Yue, Yuanlei"},{"full_name":"Bosco, Dale B","last_name":"Bosco","first_name":"Dale B"},{"last_name":"Lu","first_name":"Ying-mei","full_name":"Lu, Ying-mei"},{"full_name":"Yang, Shi-bing","last_name":"Yang","first_name":"Shi-bing"},{"first_name":"Ralf H.","last_name":"Adams","full_name":"Adams, Ralf H."},{"full_name":"Lindner, Volkhard","last_name":"Lindner","first_name":"Volkhard"},{"first_name":"Fen","last_name":"Huang","full_name":"Huang, Fen"},{"last_name":"Wu","first_name":"Long-Jun","full_name":"Wu, Long-Jun"},{"last_name":"Zheng","first_name":"Hui","full_name":"Zheng, Hui"},{"first_name":"Feng","last_name":"Han","full_name":"Han, Feng"},{"full_name":"Hippenmeyer, Simon","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061"},{"full_name":"Stowe, Ann M.","first_name":"Ann M.","last_name":"Stowe"},{"full_name":"Peng, Bo","first_name":"Bo","last_name":"Peng"},{"first_name":"Marta","last_name":"Margeta","full_name":"Margeta, Marta"},{"last_name":"Wang","first_name":"Xiaoqun","full_name":"Wang, Xiaoqun"},{"full_name":"Liu, Qiang","last_name":"Liu","first_name":"Qiang"},{"full_name":"Körbelin, Jakob","last_name":"Körbelin","first_name":"Jakob"},{"full_name":"Trepel, Martin","first_name":"Martin","last_name":"Trepel"},{"first_name":"Hui","last_name":"Lu","full_name":"Lu, Hui"},{"last_name":"Zhou","first_name":"Bo O.","full_name":"Zhou, Bo O."},{"first_name":"Hu","last_name":"Zhao","full_name":"Zhao, Hu"},{"first_name":"Wenzhi","last_name":"Su","full_name":"Su, Wenzhi"},{"last_name":"Bachoo","first_name":"Robert M.","full_name":"Bachoo, Robert M."},{"last_name":"Ge","first_name":"Woo-ping","full_name":"Ge, Woo-ping"}],"oa_version":"Preprint","date_created":"2020-10-06T08:58:59Z","date_updated":"2021-01-12T08:20:19Z","year":"2020","_id":"8616","acknowledgement":"The project was initiated in the Jan lab at UCSF. We thank Lily Jan and Yuh-Nung Jan’s generous support. We thank Liqun Luo’s lab for providing MADM-7 mice and Rolf A Brekken for VEGF-antibodies. Drs. Yuanquan Song (UPenn), Zhaozhu Hu (JHU), Ji Hu (ShanghaiTech), Yang Xiang (U. Mass), Hao Wang (Zhejiang U.) and Ruikang Wang (U. Washington) for critical input, colleagues at Children’s Research Institute, Departments of Neuroscience, Neurology and Neurotherapeutics, Pediatrics from UT Southwestern, and colleagues from the Jan lab for discussion. Dr. Bridget Samuels, Sean Morrison (UT Southwestern), and Nannan Lu (Zhejiang U.) for critical reading. We acknowledge the assistance of the CIBR Imaging core. We also thank UT Southwestern Live Cell Imaging Facility, a Shared Resource of the Harold C. Simmons Cancer Center, supported in part by an NCI Cancer Center Support Grant, P30 CA142543K. This work is supported by CIBR funds and the American Heart Association AWRP Summer 2016 Innovative Research Grant (17IRG33410377) to W-P.G.; National Natural Science Foundation of China (No.81370031) to Z.Z.;National Key Research and Development Program of China (2016YFE0125400)to F.H.;National Natural Science Foundations of China (No. 81473202) to Y.L.; National Natural Science Foundation of China (No.31600839) and Shenzhen Science and Technology Research Program (JCYJ20170818163320865) to B.P.; National Natural Science Foundation of China (No. 31800864) and Westlake University start-up funds to J-M. J. NIH R01NS088627 to W.L.J.; NIH: R01 AG020670 and RF1AG054111 to H.Z.; R01 NS088555 to A.M.S., and European Research Council No.725780 to S.H.;W-P.G. was a recipient of Bugher-American Heart Association Dan Adams Thinking Outside the Box Award.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"SiHi"}],"publisher":"Cold Spring Harbor Laboratory","publication_status":"submitted","status":"public","title":"Reduction of neuronal activity mediated by blood-vessel regression in the brain","article_processing_charge":"No","day":"15","month":"09","doi":"10.1101/2020.09.15.262782","date_published":"2020-09-15T00:00:00Z","language":[{"iso":"eng"}],"oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.09.15.262782"}],"citation":{"ama":"Gao X, Li J-L, Chen X, et al. Reduction of neuronal activity mediated by blood-vessel regression in the brain. bioRxiv. doi:10.1101/2020.09.15.262782","apa":"Gao, X., Li, J.-L., Chen, X., Ci, B., Chen, F., Lu, N., … Ge, W. (n.d.). Reduction of neuronal activity mediated by blood-vessel regression in the brain. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.09.15.262782","ieee":"X. Gao et al., “Reduction of neuronal activity mediated by blood-vessel regression in the brain,” bioRxiv. Cold Spring Harbor Laboratory.","ista":"Gao X, Li J-L, Chen X, Ci B, Chen F, Lu N, Shen B, Zheng L, Jia J-M, Yi Y, Zhang S, Shi Y-C, Shi K, Propson NE, Huang Y, Poinsatte K, Zhang Z, Yue Y, Bosco DB, Lu Y, Yang S, Adams RH, Lindner V, Huang F, Wu L-J, Zheng H, Han F, Hippenmeyer S, Stowe AM, Peng B, Margeta M, Wang X, Liu Q, Körbelin J, Trepel M, Lu H, Zhou BO, Zhao H, Su W, Bachoo RM, Ge W. Reduction of neuronal activity mediated by blood-vessel regression in the brain. bioRxiv, 10.1101/2020.09.15.262782.","short":"X. Gao, J.-L. Li, X. Chen, B. Ci, F. Chen, N. Lu, B. Shen, L. Zheng, J.-M. Jia, Y. Yi, S. Zhang, Y.-C. Shi, K. Shi, N.E. Propson, Y. Huang, K. Poinsatte, Z. Zhang, Y. Yue, D.B. Bosco, Y. Lu, S. Yang, R.H. Adams, V. Lindner, F. Huang, L.-J. Wu, H. Zheng, F. Han, S. Hippenmeyer, A.M. Stowe, B. Peng, M. Margeta, X. Wang, Q. Liu, J. Körbelin, M. Trepel, H. Lu, B.O. Zhou, H. Zhao, W. Su, R.M. Bachoo, W. Ge, BioRxiv (n.d.).","mla":"Gao, Xiaofei, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel Regression in the Brain.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.09.15.262782.","chicago":"Gao, Xiaofei, Jun-Liszt Li, Xingjun Chen, Bo Ci, Fei Chen, Nannan Lu, Bo Shen, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel Regression in the Brain.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.09.15.262782."},"publication":"bioRxiv","project":[{"grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}]},{"type":"journal_article","issue":"3","abstract":[{"text":"Mosaic analysis with double markers (MADM) technology enables concomitant fluorescent cell labeling and induction of uniparental chromosome disomy (UPD) with single-cell resolution. In UPD, imprinted genes are either overexpressed 2-fold or are not expressed. Here, the MADM platform is utilized to probe imprinting phenotypes at the transcriptional level. This protocol highlights major steps for the generation and isolation of projection neurons and astrocytes with MADM-induced UPD from mouse cerebral cortex for downstream single-cell and low-input sample RNA-sequencing experiments.\r\n\r\nFor complete details on the use and execution of this protocol, please refer to Laukoter et al. (2020b).","lang":"eng"}],"intvolume":" 1","status":"public","ddc":["570"],"title":"Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"8978","oa_version":"Published Version","file":[{"file_name":"2020_STARProtocols_Laukoter.pdf","access_level":"open_access","content_type":"application/pdf","file_size":4031449,"creator":"dernst","relation":"main_file","file_id":"8996","date_updated":"2021-01-07T15:57:27Z","date_created":"2021-01-07T15:57:27Z","checksum":"f1e9a433e9cb0f41f7b6df6b76db1f6e","success":1}],"has_accepted_license":"1","article_processing_charge":"No","day":"18","article_type":"original","citation":{"short":"S. Laukoter, N. Amberg, F. Pauler, S. Hippenmeyer, STAR Protocols 1 (2020).","mla":"Laukoter, Susanne, et al. “Generation and Isolation of Single Cells from Mouse Brain with Mosaic Analysis with Double Markers-Induced Uniparental Chromosome Disomy.” STAR Protocols, vol. 1, no. 3, 100215, Elsevier, 2020, doi:10.1016/j.xpro.2020.100215.","chicago":"Laukoter, Susanne, Nicole Amberg, Florian Pauler, and Simon Hippenmeyer. “Generation and Isolation of Single Cells from Mouse Brain with Mosaic Analysis with Double Markers-Induced Uniparental Chromosome Disomy.” STAR Protocols. Elsevier, 2020. https://doi.org/10.1016/j.xpro.2020.100215.","ama":"Laukoter S, Amberg N, Pauler F, Hippenmeyer S. Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy. STAR Protocols. 2020;1(3). doi:10.1016/j.xpro.2020.100215","apa":"Laukoter, S., Amberg, N., Pauler, F., & Hippenmeyer, S. (2020). Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2020.100215","ieee":"S. Laukoter, N. Amberg, F. Pauler, and S. Hippenmeyer, “Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy,” STAR Protocols, vol. 1, no. 3. Elsevier, 2020.","ista":"Laukoter S, Amberg N, Pauler F, Hippenmeyer S. 2020. Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy. STAR Protocols. 1(3), 100215."},"publication":"STAR Protocols","date_published":"2020-12-18T00:00:00Z","article_number":"100215","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","ec_funded":1,"file_date_updated":"2021-01-07T15:57:27Z","department":[{"_id":"SiHi"}],"publisher":"Elsevier","publication_status":"published","pmid":1,"acknowledgement":"This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Bioimaging (BIF) and Preclinical Facilities (PCF). N.A received support from the FWF Firnberg-Programm (T 1031). This work was also supported by IST Austria institutional funds; FWF SFB F78 to S.H.; NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) to S.H.; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 618444 to S.H.; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro) to S.H.","year":"2020","volume":1,"date_updated":"2021-01-12T08:21:36Z","date_created":"2020-12-30T10:17:07Z","author":[{"full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","last_name":"Laukoter","first_name":"Susanne"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","first_name":"Nicole","last_name":"Amberg","full_name":"Amberg, Nicole"},{"full_name":"Pauler, Florian","first_name":"Florian","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"}],"publication_identifier":{"issn":["2666-1667"]},"month":"12","project":[{"grant_number":"T0101031","_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Role of Eed in neural stem cell lineage progression"},{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F07805","name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression"},{"_id":"25D92700-B435-11E9-9278-68D0E5697425","grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain"},{"grant_number":"618444","_id":"25D61E48-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780"}],"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"external_id":{"pmid":["33377108"]},"oa":1,"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"doi":"10.1016/j.xpro.2020.100215"},{"quality_controlled":"1","isi":1,"project":[{"call_identifier":"FWF","name":"Role of Eed in neural stem cell lineage progression","_id":"268F8446-B435-11E9-9278-68D0E5697425","grant_number":"T0101031"},{"call_identifier":"FWF","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex","_id":"264E56E2-B435-11E9-9278-68D0E5697425","grant_number":"M02416"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"_id":"25D92700-B435-11E9-9278-68D0E5697425","grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000551459000005"]},"acknowledged_ssus":[{"_id":"PreCl"}],"language":[{"iso":"eng"}],"doi":"10.1038/s41467-019-14077-2","month":"01","publication_identifier":{"issn":["2041-1723"]},"publication_status":"published","department":[{"_id":"SiHi"}],"publisher":"Springer Nature","year":"2020","date_created":"2020-01-11T10:42:48Z","date_updated":"2023-08-17T14:23:41Z","volume":11,"author":[{"full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7903-3010","first_name":"Susanne","last_name":"Laukoter"},{"id":"2E26DF60-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8483-8753","first_name":"Robert J","last_name":"Beattie","full_name":"Beattie, Robert J"},{"orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","first_name":"Florian","full_name":"Pauler, Florian"},{"full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","first_name":"Nicole"},{"last_name":"Nakayama","first_name":"Keiichi I.","full_name":"Nakayama, Keiichi I."},{"full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"link":[{"url":"https://ist.ac.at/en/news/new-function-for-potential-tumour-suppressor-in-brain-development/","relation":"press_release","description":"News on IST Homepage"}]},"article_number":"195","file_date_updated":"2020-07-14T12:47:54Z","ec_funded":1,"article_type":"original","publication":"Nature Communications","citation":{"ista":"Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. 2020. Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Nature Communications. 11, 195.","apa":"Laukoter, S., Beattie, R. J., Pauler, F., Amberg, N., Nakayama, K. I., & Hippenmeyer, S. (2020). Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-019-14077-2","ieee":"S. Laukoter, R. J. Beattie, F. Pauler, N. Amberg, K. I. Nakayama, and S. Hippenmeyer, “Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development,” Nature Communications, vol. 11. Springer Nature, 2020.","ama":"Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development. Nature Communications. 2020;11. doi:10.1038/s41467-019-14077-2","chicago":"Laukoter, Susanne, Robert J Beattie, Florian Pauler, Nicole Amberg, Keiichi I. Nakayama, and Simon Hippenmeyer. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications. Springer Nature, 2020. https://doi.org/10.1038/s41467-019-14077-2.","mla":"Laukoter, Susanne, et al. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications, vol. 11, 195, Springer Nature, 2020, doi:10.1038/s41467-019-14077-2.","short":"S. Laukoter, R.J. Beattie, F. Pauler, N. Amberg, K.I. Nakayama, S. Hippenmeyer, Nature Communications 11 (2020)."},"date_published":"2020-01-10T00:00:00Z","scopus_import":"1","day":"10","has_accepted_license":"1","article_processing_charge":"No","title":"Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development","ddc":["570"],"status":"public","intvolume":" 11","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7253","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"7261","checksum":"ebf1ed522f4e0be8d94c939c1806a709","date_created":"2020-01-13T07:42:31Z","date_updated":"2020-07-14T12:47:54Z","access_level":"open_access","file_name":"2020_NatureComm_Laukoter.pdf","content_type":"application/pdf","file_size":8063333,"creator":"dernst"}],"type":"journal_article","abstract":[{"text":"The cyclin-dependent kinase inhibitor p57KIP2 is encoded by the imprinted Cdkn1c locus, exhibits maternal expression, and is essential for cerebral cortex development. How Cdkn1c regulates corticogenesis is however not clear. To this end we employ Mosaic Analysis with Double Markers (MADM) technology to genetically dissect Cdkn1c gene function in corticogenesis at single cell resolution. We find that the previously described growth-inhibitory Cdkn1c function is a non-cell-autonomous one, acting on the whole organism. In contrast we reveal a growth-promoting cell-autonomous Cdkn1c function which at the mechanistic level mediates radial glial progenitor cell and nascent projection neuron survival. Strikingly, the growth-promoting function of Cdkn1c is highly dosage sensitive but not subject to genomic imprinting. Collectively, our results suggest that the Cdkn1c locus regulates cortical development through distinct cell-autonomous and non-cell-autonomous mechanisms. More generally, our study highlights the importance to probe the relative contributions of cell intrinsic gene function and tissue-wide mechanisms to the overall phenotype.","lang":"eng"}]},{"file_date_updated":"2020-09-24T07:03:20Z","article_number":"51512","author":[{"first_name":"Hyang Mi","last_name":"Moon","full_name":"Moon, Hyang Mi"},{"full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Luo, Liqun","first_name":"Liqun","last_name":"Luo"},{"full_name":"Wynshaw-Boris, Anthony","last_name":"Wynshaw-Boris","first_name":"Anthony"}],"volume":9,"date_updated":"2023-08-18T07:06:31Z","date_created":"2020-03-20T13:16:41Z","pmid":1,"year":"2020","department":[{"_id":"SiHi"}],"publisher":"eLife Sciences Publications","publication_status":"published","publication_identifier":{"issn":["2050-084X"]},"month":"03","doi":"10.7554/elife.51512","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"main_file_link":[{"url":"https://doi.org/10.1101/751958","open_access":"1"}],"oa":1,"external_id":{"pmid":["32159512"],"isi":["000522835800001"]},"isi":1,"quality_controlled":"1","abstract":[{"lang":"eng","text":"Heterozygous loss of human PAFAH1B1 (coding for LIS1) results in the disruption of neurogenesis and neuronal migration via dysregulation of microtubule (MT) stability and dynein motor function/localization that alters mitotic spindle orientation, chromosomal segregation, and nuclear migration. Recently, human induced pluripotent stem cell (iPSC) models revealed an important role for LIS1 in controlling the length of terminal cell divisions of outer radial glial (oRG) progenitors, suggesting cellular functions of LIS1 in regulating neural progenitor cell (NPC) daughter cell separation. Here we examined the late mitotic stages NPCs in vivo and mouse embryonic fibroblasts (MEFs) in vitro from Pafah1b1-deficient mutants. Pafah1b1-deficient neocortical NPCs and MEFs similarly exhibited cleavage plane displacement with mislocalization of furrow-associated markers, associated with actomyosin dysfunction and cell membrane hyper-contractility. Thus, it suggests LIS1 acts as a key molecular link connecting MTs/dynein and actomyosin, ensuring that cell membrane contractility is tightly controlled to execute proper daughter cell separation."}],"type":"journal_article","file":[{"checksum":"396ceb2dd10b102ef4e699666b9342c3","success":1,"date_created":"2020-09-24T07:03:20Z","date_updated":"2020-09-24T07:03:20Z","relation":"main_file","file_id":"8567","file_size":15089438,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"2020_elife_Moon.pdf"}],"oa_version":"Published Version","_id":"7593","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 9","title":"LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility","status":"public","ddc":["570"],"has_accepted_license":"1","article_processing_charge":"No","day":"11","scopus_import":"1","date_published":"2020-03-11T00:00:00Z","citation":{"ieee":"H. M. Moon, S. Hippenmeyer, L. Luo, and A. Wynshaw-Boris, “LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility,” eLife, vol. 9. eLife Sciences Publications, 2020.","apa":"Moon, H. M., Hippenmeyer, S., Luo, L., & Wynshaw-Boris, A. (2020). LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.51512","ista":"Moon HM, Hippenmeyer S, Luo L, Wynshaw-Boris A. 2020. LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. eLife. 9, 51512.","ama":"Moon HM, Hippenmeyer S, Luo L, Wynshaw-Boris A. LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility. eLife. 2020;9. doi:10.7554/elife.51512","chicago":"Moon, Hyang Mi, Simon Hippenmeyer, Liqun Luo, and Anthony Wynshaw-Boris. “LIS1 Determines Cleavage Plane Positioning by Regulating Actomyosin-Mediated Cell Membrane Contractility.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/elife.51512.","short":"H.M. Moon, S. Hippenmeyer, L. Luo, A. Wynshaw-Boris, ELife 9 (2020).","mla":"Moon, Hyang Mi, et al. “LIS1 Determines Cleavage Plane Positioning by Regulating Actomyosin-Mediated Cell Membrane Contractility.” ELife, vol. 9, 51512, eLife Sciences Publications, 2020, doi:10.7554/elife.51512."},"publication":"eLife","article_type":"original"},{"oa_version":"Published Version","file":[{"file_id":"10398","relation":"main_file","date_updated":"2021-12-02T12:35:12Z","date_created":"2021-12-02T12:35:12Z","success":1,"checksum":"05a8e65d49c3f5b8e37ac4afe68287e2","file_name":"2020_BrJournalCancer_Hippe.pdf","access_level":"open_access","creator":"cchlebak","content_type":"application/pdf","file_size":3620691}],"intvolume":" 123","title":"EGFR/Ras-induced CCL20 production modulates the tumour microenvironment","ddc":["610"],"status":"public","_id":"8093","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","abstract":[{"lang":"eng","text":"Background: The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.\r\nMethods: The effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo.\r\nResults: Tumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system.\r\nConclusion: We propose that the chemokine axis CCL20–CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy."}],"type":"journal_article","date_published":"2020-09-15T00:00:00Z","page":"942-954","article_type":"original","citation":{"apa":"Hippe, A., Braun, S. A., Oláh, P., Gerber, P. A., Schorr, A., Seeliger, S., … Homey, B. (2020). EGFR/Ras-induced CCL20 production modulates the tumour microenvironment. British Journal of Cancer. Springer Nature. https://doi.org/10.1038/s41416-020-0943-2","ieee":"A. Hippe et al., “EGFR/Ras-induced CCL20 production modulates the tumour microenvironment,” British Journal of Cancer, vol. 123. Springer Nature, pp. 942–954, 2020.","ista":"Hippe A, Braun SA, Oláh P, Gerber PA, Schorr A, Seeliger S, Holtz S, Jannasch K, Pivarcsi A, Buhren B, Schrumpf H, Kislat A, Bünemann E, Steinhoff M, Fischer J, Lira SA, Boukamp P, Hevezi P, Stoecklein NH, Hoffmann T, Alves F, Sleeman J, Bauer T, Klufa J, Amberg N, Sibilia M, Zlotnik A, Müller-Homey A, Homey B. 2020. EGFR/Ras-induced CCL20 production modulates the tumour microenvironment. British Journal of Cancer. 123, 942–954.","ama":"Hippe A, Braun SA, Oláh P, et al. EGFR/Ras-induced CCL20 production modulates the tumour microenvironment. British Journal of Cancer. 2020;123:942-954. doi:10.1038/s41416-020-0943-2","chicago":"Hippe, Andreas, Stephan Alexander Braun, Péter Oláh, Peter Arne Gerber, Anne Schorr, Stephan Seeliger, Stephanie Holtz, et al. “EGFR/Ras-Induced CCL20 Production Modulates the Tumour Microenvironment.” British Journal of Cancer. Springer Nature, 2020. https://doi.org/10.1038/s41416-020-0943-2.","short":"A. Hippe, S.A. Braun, P. Oláh, P.A. Gerber, A. Schorr, S. Seeliger, S. Holtz, K. Jannasch, A. Pivarcsi, B. Buhren, H. Schrumpf, A. Kislat, E. Bünemann, M. Steinhoff, J. Fischer, S.A. Lira, P. Boukamp, P. Hevezi, N.H. Stoecklein, T. Hoffmann, F. Alves, J. Sleeman, T. Bauer, J. Klufa, N. Amberg, M. Sibilia, A. Zlotnik, A. Müller-Homey, B. Homey, British Journal of Cancer 123 (2020) 942–954.","mla":"Hippe, Andreas, et al. “EGFR/Ras-Induced CCL20 Production Modulates the Tumour Microenvironment.” British Journal of Cancer, vol. 123, Springer Nature, 2020, pp. 942–54, doi:10.1038/s41416-020-0943-2."},"publication":"British Journal of Cancer","has_accepted_license":"1","article_processing_charge":"No","day":"15","scopus_import":"1","volume":123,"date_updated":"2023-08-22T07:51:12Z","date_created":"2020-07-05T22:00:46Z","related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1038/s41416-021-01563-y"}],"record":[{"id":"10170","relation":"later_version","status":"deleted"}]},"author":[{"full_name":"Hippe, Andreas","first_name":"Andreas","last_name":"Hippe"},{"full_name":"Braun, Stephan Alexander","last_name":"Braun","first_name":"Stephan Alexander"},{"full_name":"Oláh, Péter","last_name":"Oláh","first_name":"Péter"},{"full_name":"Gerber, Peter Arne","first_name":"Peter Arne","last_name":"Gerber"},{"full_name":"Schorr, Anne","first_name":"Anne","last_name":"Schorr"},{"full_name":"Seeliger, Stephan","last_name":"Seeliger","first_name":"Stephan"},{"first_name":"Stephanie","last_name":"Holtz","full_name":"Holtz, Stephanie"},{"full_name":"Jannasch, Katharina","first_name":"Katharina","last_name":"Jannasch"},{"full_name":"Pivarcsi, Andor","first_name":"Andor","last_name":"Pivarcsi"},{"first_name":"Bettina","last_name":"Buhren","full_name":"Buhren, Bettina"},{"last_name":"Schrumpf","first_name":"Holger","full_name":"Schrumpf, Holger"},{"last_name":"Kislat","first_name":"Andreas","full_name":"Kislat, Andreas"},{"full_name":"Bünemann, Erich","first_name":"Erich","last_name":"Bünemann"},{"full_name":"Steinhoff, Martin","last_name":"Steinhoff","first_name":"Martin"},{"full_name":"Fischer, Jens","first_name":"Jens","last_name":"Fischer"},{"first_name":"Sérgio A.","last_name":"Lira","full_name":"Lira, Sérgio A."},{"first_name":"Petra","last_name":"Boukamp","full_name":"Boukamp, Petra"},{"last_name":"Hevezi","first_name":"Peter","full_name":"Hevezi, Peter"},{"full_name":"Stoecklein, Nikolas Hendrik","last_name":"Stoecklein","first_name":"Nikolas Hendrik"},{"last_name":"Hoffmann","first_name":"Thomas","full_name":"Hoffmann, Thomas"},{"full_name":"Alves, Frauke","first_name":"Frauke","last_name":"Alves"},{"full_name":"Sleeman, Jonathan","last_name":"Sleeman","first_name":"Jonathan"},{"full_name":"Bauer, Thomas","last_name":"Bauer","first_name":"Thomas"},{"full_name":"Klufa, Jörg","last_name":"Klufa","first_name":"Jörg"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","first_name":"Nicole","last_name":"Amberg","full_name":"Amberg, Nicole"},{"full_name":"Sibilia, Maria","last_name":"Sibilia","first_name":"Maria"},{"full_name":"Zlotnik, Albert","last_name":"Zlotnik","first_name":"Albert"},{"last_name":"Müller-Homey","first_name":"Anja","full_name":"Müller-Homey, Anja"},{"last_name":"Homey","first_name":"Bernhard","full_name":"Homey, Bernhard"}],"publisher":"Springer Nature","department":[{"_id":"SiHi"}],"publication_status":"published","pmid":1,"year":"2020","acknowledgement":"The authors would like to thank A. van Lierop for technical assistance. In addition, we thank C. Dullin, J. Missbach-Güntner and S. Greco for advice and assistance with fpVCT imaging. Furthermore, the authors would like to thank H. K. Horst for advice on performing matrigel plug assays. This study has also been partially presented in A. Schorr’s doctoral thesis and the funding report of the SPP 1190 ‘The tumor-vessel interface’ of the ‘Deutsche Forschungsgemeinschaft’ (DFG).\r\nThis project was funded by the SPP 1190 “The tumor-vessel interface” and HO 2092/8-1 of the ‘Deutsche Forschungsgemeinschaft’ (DFG) to B. Homey. In addition, it was supported by grants from the Austrian Science Fund (FWF, W1212 to N. Amberg and J. Klufa and I4300-B to T. Bauer), the WWTF project LS16-025 and the European Research Council (ERC) Advanced grant (ERC-2015-AdG TNT-Tumors 694883) to M. Sibilia.","file_date_updated":"2021-12-02T12:35:12Z","language":[{"iso":"eng"}],"doi":"10.1038/s41416-020-0943-2","quality_controlled":"1","isi":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000544152500001"],"pmid":["32601464"]},"oa":1,"publication_identifier":{"eissn":["1532-1827"],"issn":["0007-0920"]},"month":"09"},{"publication_identifier":{"issn":["0896-6273"]},"month":"09","project":[{"name":"Molecular Mechanisms of Radial Neuronal Migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812"},{"_id":"268F8446-B435-11E9-9278-68D0E5697425","grant_number":"T0101031","name":"Role of Eed in neural stem cell lineage progression","call_identifier":"FWF"},{"name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex","call_identifier":"FWF","grant_number":"M02416","_id":"264E56E2-B435-11E9-9278-68D0E5697425"},{"grant_number":"LS13-002","_id":"25D92700-B435-11E9-9278-68D0E5697425","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain"},{"name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level","grant_number":"RGP0053/2014","_id":"25D7962E-B435-11E9-9278-68D0E5697425"},{"_id":"25D61E48-B435-11E9-9278-68D0E5697425","grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","isi":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"external_id":{"isi":["000579698700006"]},"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"doi":"10.1016/j.neuron.2020.06.031","ec_funded":1,"file_date_updated":"2020-12-02T09:26:46Z","department":[{"_id":"SiHi"}],"publisher":"Elsevier","publication_status":"published","year":"2020","acknowledgement":"We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), and A. Seitz and P. Moll (Lexogen GmbH) for technical support; G. Arque, S. Resch, C. Igler, C. Dotter, C. Yahya, Q. Hudson, and D. Andergassen for initial experiments and/or assistance; D. Barlow, O. Bell, and all members of the Hippenmeyer lab for discussion; and N. Barton, B. Vicoso, M. Sixt, and L. Luo for comments on earlier versions of the manuscript. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facilities (BIF), Life Science Facilities (LSF), and Preclinical Facilities (PCF). A.H.H. is a recipient of a DOC fellowship (24812) of the Austrian Academy of Sciences. N.A. received support from the FWF Firnberg-Programm (T 1031). R.B. received support from the FWF Meitner-Programm (M 2416). This work was also supported by IST Austria institutional funds; a NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) to S.H.; a program grant from the Human Frontiers Science Program (RGP0053/2014) to S.H.; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement 618444 to S.H.; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 725780 LinPro) to S.H.","volume":107,"date_created":"2020-07-23T16:03:12Z","date_updated":"2023-08-22T08:20:11Z","related_material":{"link":[{"relation":"press_release","description":"News on IST Website","url":"https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/"}]},"author":[{"first_name":"Susanne","last_name":"Laukoter","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7462-0048","first_name":"Florian","last_name":"Pauler","full_name":"Pauler, Florian"},{"full_name":"Beattie, Robert J","last_name":"Beattie","first_name":"Robert J","orcid":"0000-0002-8483-8753","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Nicole","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole"},{"full_name":"Hansen, Andi H","first_name":"Andi H","last_name":"Hansen","id":"38853E16-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Streicher, Carmen","first_name":"Carmen","last_name":"Streicher","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Penz, Thomas","first_name":"Thomas","last_name":"Penz"},{"orcid":"0000-0001-6091-3088","last_name":"Bock","first_name":"Christoph","full_name":"Bock, Christoph"},{"first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"}],"scopus_import":"1","article_processing_charge":"No","has_accepted_license":"1","day":"23","page":"1160-1179.e9","article_type":"original","citation":{"short":"S. Laukoter, F. Pauler, R.J. Beattie, N. Amberg, A.H. Hansen, C. Streicher, T. Penz, C. Bock, S. Hippenmeyer, Neuron 107 (2020) 1160–1179.e9.","mla":"Laukoter, Susanne, et al. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” Neuron, vol. 107, no. 6, Elsevier, 2020, p. 1160–1179.e9, doi:10.1016/j.neuron.2020.06.031.","chicago":"Laukoter, Susanne, Florian Pauler, Robert J Beattie, Nicole Amberg, Andi H Hansen, Carmen Streicher, Thomas Penz, Christoph Bock, and Simon Hippenmeyer. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.06.031.","ama":"Laukoter S, Pauler F, Beattie RJ, et al. Cell-type specificity of genomic imprinting in cerebral cortex. Neuron. 2020;107(6):1160-1179.e9. doi:10.1016/j.neuron.2020.06.031","ieee":"S. Laukoter et al., “Cell-type specificity of genomic imprinting in cerebral cortex,” Neuron, vol. 107, no. 6. Elsevier, p. 1160–1179.e9, 2020.","apa":"Laukoter, S., Pauler, F., Beattie, R. J., Amberg, N., Hansen, A. H., Streicher, C., … Hippenmeyer, S. (2020). Cell-type specificity of genomic imprinting in cerebral cortex. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.06.031","ista":"Laukoter S, Pauler F, Beattie RJ, Amberg N, Hansen AH, Streicher C, Penz T, Bock C, Hippenmeyer S. 2020. Cell-type specificity of genomic imprinting in cerebral cortex. Neuron. 107(6), 1160–1179.e9."},"publication":"Neuron","date_published":"2020-09-23T00:00:00Z","type":"journal_article","issue":"6","abstract":[{"lang":"eng","text":"In mammalian genomes, a subset of genes is regulated by genomic imprinting, resulting in silencing of one parental allele. Imprinting is essential for cerebral cortex development, but prevalence and functional impact in individual cells is unclear. Here, we determined allelic expression in cortical cell types and established a quantitative platform to interrogate imprinting in single cells. We created cells with uniparental chromosome disomy (UPD) containing two copies of either the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold overexpressed or not expressed. By genetic labeling of UPD, we determined cellular phenotypes and transcriptional responses to deregulated imprinted gene expression at unprecedented single-cell resolution. We discovered an unexpected degree of cell-type specificity and a novel function of imprinting in the regulation of cortical astrocyte survival. More generally, our results suggest functional relevance of imprinted gene expression in glial astrocyte lineage and thus for generating cortical cell-type diversity."}],"intvolume":" 107","status":"public","title":"Cell-type specificity of genomic imprinting in cerebral cortex","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"8162","file":[{"success":1,"checksum":"7becdc16a6317304304631087ae7dd7f","date_created":"2020-12-02T09:26:46Z","date_updated":"2020-12-02T09:26:46Z","file_id":"8828","relation":"main_file","creator":"dernst","content_type":"application/pdf","file_size":8911830,"access_level":"open_access","file_name":"2020_Neuron_Laukoter.pdf"}],"oa_version":"Published Version"},{"external_id":{"isi":["000573860700001"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"isi":1,"quality_controlled":"1","project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780"}],"doi":"10.1002/advs.202001724","language":[{"iso":"eng"}],"month":"11","publication_identifier":{"issn":["2198-3844"]},"acknowledgement":"The authors thank Drs. J. Eisen, QR. Lu, S. Duan, Z‐H. Li, W. Mo, and Q. Wu for their critical comments on the manuscript. They also thank Dr. H. Zong for providing the CKO_NG2‐CreER model. This work is supported by the National Key Research and Development Program of China, Stem Cell and Translational Research (2016YFA0101201 to C.L., 2016YFA0100303 to Y.J.W.), the National Natural Science Foundation of China (81673035 and 81972915 to C.L., 81472722 to Y.J.W.), the Science Foundation for Distinguished Young Scientists of Zhejiang Province (LR17H160001 to C.L.), Fundamental Research Funds for the Central Universities (2016QNA7023 and 2017QNA7028 to C.L.) and the Thousand Talent Program for Young Outstanding Scientists, China (to C.L.), IST Austria institutional funds (to S.H.), European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (725780 LinPro to S.H.). C.L. is a scholar of K. C. Wong Education Foundation.","year":"2020","publication_status":"published","department":[{"_id":"SiHi"}],"publisher":"Wiley","author":[{"full_name":"Tian, Anhao","last_name":"Tian","first_name":"Anhao"},{"full_name":"Kang, Bo","last_name":"Kang","first_name":"Bo"},{"full_name":"Li, Baizhou","first_name":"Baizhou","last_name":"Li"},{"first_name":"Biying","last_name":"Qiu","full_name":"Qiu, Biying"},{"first_name":"Wenhong","last_name":"Jiang","full_name":"Jiang, Wenhong"},{"last_name":"Shao","first_name":"Fangjie","full_name":"Shao, Fangjie"},{"full_name":"Gao, Qingqing","last_name":"Gao","first_name":"Qingqing"},{"full_name":"Liu, Rui","first_name":"Rui","last_name":"Liu"},{"last_name":"Cai","first_name":"Chengwei","full_name":"Cai, Chengwei"},{"last_name":"Jing","first_name":"Rui","full_name":"Jing, Rui"},{"last_name":"Wang","first_name":"Wei","full_name":"Wang, Wei"},{"first_name":"Pengxiang","last_name":"Chen","full_name":"Chen, Pengxiang"},{"first_name":"Qinghui","last_name":"Liang","full_name":"Liang, Qinghui"},{"last_name":"Bao","first_name":"Lili","full_name":"Bao, Lili"},{"full_name":"Man, Jianghong","first_name":"Jianghong","last_name":"Man"},{"last_name":"Wang","first_name":"Yan","full_name":"Wang, Yan"},{"first_name":"Yu","last_name":"Shi","full_name":"Shi, Yu"},{"full_name":"Li, Jin","first_name":"Jin","last_name":"Li"},{"last_name":"Yang","first_name":"Minmin","full_name":"Yang, Minmin"},{"full_name":"Wang, Lisha","last_name":"Wang","first_name":"Lisha"},{"first_name":"Jianmin","last_name":"Zhang","full_name":"Zhang, Jianmin"},{"full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Zhu","first_name":"Junming","full_name":"Zhu, Junming"},{"full_name":"Bian, Xiuwu","last_name":"Bian","first_name":"Xiuwu"},{"last_name":"Wang","first_name":"Ying‐Jie","full_name":"Wang, Ying‐Jie"},{"full_name":"Liu, Chong","last_name":"Liu","first_name":"Chong"}],"date_updated":"2023-08-22T09:53:01Z","date_created":"2020-10-01T09:44:13Z","volume":7,"article_number":"2001724","file_date_updated":"2020-12-10T14:07:24Z","ec_funded":1,"publication":"Advanced Science","citation":{"ieee":"A. Tian et al., “Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting,” Advanced Science, vol. 7, no. 21. Wiley, 2020.","apa":"Tian, A., Kang, B., Li, B., Qiu, B., Jiang, W., Shao, F., … Liu, C. (2020). Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting. Advanced Science. Wiley. https://doi.org/10.1002/advs.202001724","ista":"Tian A, Kang B, Li B, Qiu B, Jiang W, Shao F, Gao Q, Liu R, Cai C, Jing R, Wang W, Chen P, Liang Q, Bao L, Man J, Wang Y, Shi Y, Li J, Yang M, Wang L, Zhang J, Hippenmeyer S, Zhu J, Bian X, Wang Y, Liu C. 2020. Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting. Advanced Science. 7(21), 2001724.","ama":"Tian A, Kang B, Li B, et al. Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting. Advanced Science. 2020;7(21). doi:10.1002/advs.202001724","chicago":"Tian, Anhao, Bo Kang, Baizhou Li, Biying Qiu, Wenhong Jiang, Fangjie Shao, Qingqing Gao, et al. “Oncogenic State and Cell Identity Combinatorially Dictate the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.” Advanced Science. Wiley, 2020. https://doi.org/10.1002/advs.202001724.","short":"A. Tian, B. Kang, B. Li, B. Qiu, W. Jiang, F. Shao, Q. Gao, R. Liu, C. Cai, R. Jing, W. Wang, P. Chen, Q. Liang, L. Bao, J. Man, Y. Wang, Y. Shi, J. Li, M. Yang, L. Wang, J. Zhang, S. Hippenmeyer, J. Zhu, X. Bian, Y. Wang, C. Liu, Advanced Science 7 (2020).","mla":"Tian, Anhao, et al. “Oncogenic State and Cell Identity Combinatorially Dictate the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.” Advanced Science, vol. 7, no. 21, 2001724, Wiley, 2020, doi:10.1002/advs.202001724."},"article_type":"original","date_published":"2020-11-04T00:00:00Z","keyword":["General Engineering","General Physics and Astronomy","General Materials Science","Medicine (miscellaneous)","General Chemical Engineering","Biochemistry","Genetics and Molecular Biology (miscellaneous)"],"day":"04","article_processing_charge":"No","has_accepted_license":"1","_id":"8592","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting","ddc":["570"],"status":"public","intvolume":" 7","oa_version":"Published Version","file":[{"file_name":"2020_AdvScience_Tian.pdf","access_level":"open_access","creator":"dernst","file_size":7835833,"content_type":"application/pdf","file_id":"8938","relation":"main_file","date_created":"2020-12-10T14:07:24Z","date_updated":"2020-12-10T14:07:24Z","success":1,"checksum":"92818c23ecc70e35acfa671f3cfb9909"}],"type":"journal_article","abstract":[{"text":"Glioblastoma is the most malignant cancer in the brain and currently incurable. It is urgent to identify effective targets for this lethal disease. Inhibition of such targets should suppress the growth of cancer cells and, ideally also precancerous cells for early prevention, but minimally affect their normal counterparts. Using genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility of cells within the development hierarchy of glioma to the knockout of insulin‐like growth factor I receptor (IGF1R) is determined not only by their oncogenic states, but also by their cell identities/states. Knockout of IGF1R selectively disrupts the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable outcome of IGF1R knockout on cell growth requires the mutant cells to commit to the OPC identity regardless of its development hierarchical status. At the molecular level, oncogenic mutations reprogram the cellular network of OPCs and force them to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed. The findings reveal the cellular window of IGF1R targeting and establish IGF1R as an effective target for the prevention and treatment of glioblastoma.","lang":"eng"}],"issue":"21"}]