--- _id: '8544' 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. 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Südhof and J.I. Morgan for Cbln1fl mice, L. Anderson for help in generating the MADM alleles, W. Joo for a previously unpublished construct, M. Yuzaki, K. Shen, J. Ding, and members of the Luo lab, including J.M. Kebschull, H. Li, J. Li, T. Li, C.M. McLaughlin, D. Pederick, J. Ren, D.C.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. article_processing_charge: No article_type: original author: - first_name: Yukari H. full_name: Takeo, Yukari H. last_name: Takeo - first_name: S. Andrew full_name: Shuster, S. Andrew last_name: Shuster - first_name: Linnie full_name: Jiang, Linnie last_name: Jiang - first_name: Miley full_name: Hu, Miley last_name: Hu - first_name: David J. full_name: Luginbuhl, David J. last_name: Luginbuhl - first_name: Thomas full_name: Rülicke, Thomas last_name: Rülicke - first_name: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Mark J. full_name: Wagner, Mark J. last_name: Wagner - first_name: Surya full_name: Ganguli, Surya last_name: Ganguli - first_name: Liqun full_name: Luo, Liqun last_name: Luo 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 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 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. 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. 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. 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. date_created: 2020-09-21T11:59:47Z date_published: 2021-02-17T00:00:00Z date_updated: 2024-03-06T12:12:48Z day: '17' department: - _id: SiHi doi: 10.1016/j.neuron.2020.11.028 ec_funded: 1 intvolume: ' 109' issue: '4' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2020.06.14.151258 month: '02' oa: 1 oa_version: Preprint page: P629-644.E8 project: - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication: Neuron publication_identifier: eissn: - 1097-4199 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 109 year: '2021' ... --- _id: '9962' 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. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Andi H full_name: Hansen, Andi H id: 38853E16-F248-11E8-B48F-1D18A9856A87 last_name: Hansen 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 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 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. 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. ista: Hansen AH. 2021. Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration. Institute of Science and Technology Austria. 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. date_created: 2021-08-29T12:36:50Z date_published: 2021-09-02T00:00:00Z date_updated: 2023-09-22T09:58:30Z day: '02' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: SiHi doi: 10.15479/at:ista:9962 file: - access_level: closed checksum: 66b56f5b988b233dc66a4f4b4fb2cdfe content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: ahansen date_created: 2021-08-30T09:17:39Z date_updated: 2022-09-03T22:30:04Z embargo_to: open_access file_id: '9971' file_name: Thesis_Hansen.docx file_size: 10629190 relation: source_file - access_level: open_access checksum: 204fa40321a1c6289b68c473634c4bf3 content_type: application/pdf creator: ahansen date_created: 2021-08-30T09:29:44Z date_updated: 2022-09-03T22:30:04Z embargo: 2022-09-02 file_id: '9972' file_name: Thesis_Hansen_PDFA-1a.pdf file_size: 13457469 relation: main_file file_date_updated: 2022-09-03T22:30:04Z has_accepted_license: '1' keyword: - Neuronal migration - Non-cell-autonomous - Cell-autonomous - Neurodevelopmental disease language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '182' project: - _id: 2625A13E-B435-11E9-9278-68D0E5697425 grant_number: '24812' name: Molecular Mechanisms of Radial Neuronal Migration publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '8569' relation: part_of_dissertation status: public - id: '960' relation: part_of_dissertation status: public status: public supervisor: - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 title: Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2021' ... --- _id: '7814' abstract: - lang: eng 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.' acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: PreCl - _id: EM-Fac article_number: '48' article_processing_charge: No article_type: original author: - first_name: Robert J full_name: Beattie, Robert J id: 2E26DF60-F248-11E8-B48F-1D18A9856A87 last_name: Beattie orcid: 0000-0002-8483-8753 - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler 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' 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' 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.' 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.' ista: 'Beattie RJ, Hippenmeyer S, Pauler F. 2020. SCOPES: Sparking curiosity through Open-Source platforms in education and science. Frontiers in Education. 5, 48.' 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). date_created: 2020-05-11T08:18:48Z date_published: 2020-05-08T00:00:00Z date_updated: 2021-01-12T08:15:42Z day: '08' ddc: - '570' department: - _id: SiHi doi: 10.3389/feduc.2020.00048 ec_funded: 1 file: - access_level: open_access checksum: a24ec24e38d843341ae620ec76c53688 content_type: application/pdf creator: dernst date_created: 2020-05-11T11:34:08Z date_updated: 2020-07-14T12:48:03Z file_id: '7818' file_name: 2020_FrontiersEduc_Beattie.pdf file_size: 1402146 relation: main_file file_date_updated: 2020-07-14T12:48:03Z has_accepted_license: '1' intvolume: ' 5' language: - iso: eng month: '05' oa: 1 oa_version: Published Version project: - _id: 264E56E2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: M02416 name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication: Frontiers in Education publication_identifier: issn: - 2504-284X publication_status: published publisher: Frontiers Media quality_controlled: '1' status: public title: 'SCOPES: Sparking curiosity through Open-Source platforms in education and science' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 5 year: '2020' ... --- _id: '8616' abstract: - lang: eng 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. 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.' article_processing_charge: No author: - first_name: Xiaofei full_name: Gao, Xiaofei last_name: Gao - first_name: Jun-Liszt full_name: Li, Jun-Liszt last_name: Li - first_name: Xingjun full_name: Chen, Xingjun last_name: Chen - first_name: Bo full_name: Ci, Bo last_name: Ci - first_name: Fei full_name: Chen, Fei last_name: Chen - first_name: Nannan full_name: Lu, Nannan last_name: Lu - first_name: Bo full_name: Shen, Bo last_name: Shen - first_name: Lijun full_name: Zheng, Lijun last_name: Zheng - first_name: Jie-Min full_name: Jia, Jie-Min last_name: Jia - first_name: Yating full_name: Yi, Yating last_name: Yi - first_name: Shiwen full_name: Zhang, Shiwen last_name: Zhang - first_name: Ying-Chao full_name: Shi, Ying-Chao last_name: Shi - first_name: Kaibin full_name: Shi, Kaibin last_name: Shi - first_name: Nicholas E full_name: Propson, Nicholas E last_name: Propson - first_name: Yubin full_name: Huang, Yubin last_name: Huang - first_name: Katherine full_name: Poinsatte, Katherine last_name: Poinsatte - first_name: Zhaohuan full_name: Zhang, Zhaohuan last_name: Zhang - first_name: Yuanlei full_name: Yue, Yuanlei last_name: Yue - first_name: Dale B full_name: Bosco, Dale B last_name: Bosco - first_name: Ying-mei full_name: Lu, Ying-mei last_name: Lu - first_name: Shi-bing full_name: Yang, Shi-bing last_name: Yang - first_name: Ralf H. full_name: Adams, Ralf H. last_name: Adams - first_name: Volkhard full_name: Lindner, Volkhard last_name: Lindner - first_name: Fen full_name: Huang, Fen last_name: Huang - first_name: Long-Jun full_name: Wu, Long-Jun last_name: Wu - first_name: Hui full_name: Zheng, Hui last_name: Zheng - first_name: Feng full_name: Han, Feng last_name: Han - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Ann M. full_name: Stowe, Ann M. last_name: Stowe - first_name: Bo full_name: Peng, Bo last_name: Peng - first_name: Marta full_name: Margeta, Marta last_name: Margeta - first_name: Xiaoqun full_name: Wang, Xiaoqun last_name: Wang - first_name: Qiang full_name: Liu, Qiang last_name: Liu - first_name: Jakob full_name: Körbelin, Jakob last_name: Körbelin - first_name: Martin full_name: Trepel, Martin last_name: Trepel - first_name: Hui full_name: Lu, Hui last_name: Lu - first_name: Bo O. full_name: Zhou, Bo O. last_name: Zhou - first_name: Hu full_name: Zhao, Hu last_name: Zhao - first_name: Wenzhi full_name: Su, Wenzhi last_name: Su - first_name: Robert M. full_name: Bachoo, Robert M. last_name: Bachoo - first_name: Woo-ping full_name: Ge, Woo-ping last_name: Ge 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 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. 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. 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. 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.). date_created: 2020-10-06T08:58:59Z date_published: 2020-09-15T00:00:00Z date_updated: 2021-01-12T08:20:19Z day: '15' department: - _id: SiHi doi: 10.1101/2020.09.15.262782 ec_funded: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2020.09.15.262782 month: '09' oa: 1 oa_version: Preprint project: - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory status: public title: Reduction of neuronal activity mediated by blood-vessel regression in the brain type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '8978' abstract: - lang: eng 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)." acknowledged_ssus: - _id: Bio - _id: PreCl 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. article_number: '100215' article_processing_charge: No article_type: original author: - first_name: Susanne full_name: Laukoter, Susanne id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87 last_name: Laukoter - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: 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 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. 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. 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. short: S. Laukoter, N. Amberg, F. Pauler, S. Hippenmeyer, STAR Protocols 1 (2020). date_created: 2020-12-30T10:17:07Z date_published: 2020-12-18T00:00:00Z date_updated: 2021-01-12T08:21:36Z day: '18' ddc: - '570' department: - _id: SiHi doi: 10.1016/j.xpro.2020.100215 ec_funded: 1 external_id: pmid: - '33377108' file: - access_level: open_access checksum: f1e9a433e9cb0f41f7b6df6b76db1f6e content_type: application/pdf creator: dernst date_created: 2021-01-07T15:57:27Z date_updated: 2021-01-07T15:57:27Z file_id: '8996' file_name: 2020_STARProtocols_Laukoter.pdf file_size: 4031449 relation: main_file success: 1 file_date_updated: 2021-01-07T15:57:27Z has_accepted_license: '1' intvolume: ' 1' issue: '3' language: - iso: eng month: '12' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 268F8446-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: T0101031 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 - _id: 25D61E48-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618444' name: Molecular Mechanisms of Cerebral Cortex Development - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication: STAR Protocols publication_identifier: issn: - 2666-1667 publication_status: published publisher: Elsevier quality_controlled: '1' status: public title: Generation and isolation of single cells from mouse brain with mosaic analysis with double markers-induced uniparental chromosome disomy tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 1 year: '2020' ... --- _id: '7253' abstract: - lang: eng 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. acknowledged_ssus: - _id: PreCl article_number: '195' article_processing_charge: No article_type: original author: - first_name: Susanne full_name: Laukoter, Susanne id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87 last_name: Laukoter orcid: 0000-0002-7903-3010 - first_name: Robert J full_name: Beattie, Robert J id: 2E26DF60-F248-11E8-B48F-1D18A9856A87 last_name: Beattie orcid: 0000-0002-8483-8753 - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Keiichi I. full_name: Nakayama, Keiichi I. last_name: Nakayama - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: 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 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 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. 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. 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. 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_created: 2020-01-11T10:42:48Z date_published: 2020-01-10T00:00:00Z date_updated: 2023-08-17T14:23:41Z day: '10' ddc: - '570' department: - _id: SiHi doi: 10.1038/s41467-019-14077-2 ec_funded: 1 external_id: isi: - '000551459000005' file: - access_level: open_access checksum: ebf1ed522f4e0be8d94c939c1806a709 content_type: application/pdf creator: dernst date_created: 2020-01-13T07:42:31Z date_updated: 2020-07-14T12:47:54Z file_id: '7261' file_name: 2020_NatureComm_Laukoter.pdf file_size: 8063333 relation: main_file file_date_updated: 2020-07-14T12:47:54Z has_accepted_license: '1' intvolume: ' 11' isi: 1 language: - iso: eng month: '01' oa: 1 oa_version: Published Version project: - _id: 268F8446-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: T0101031 name: Role of Eed in neural stem cell lineage progression - _id: 264E56E2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: M02416 name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' 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 publication: Nature Communications publication_identifier: issn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/new-function-for-potential-tumour-suppressor-in-brain-development/ scopus_import: '1' status: public title: Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2020' ... --- _id: '7593' 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. article_number: '51512' article_processing_charge: No article_type: original author: - first_name: Hyang Mi full_name: Moon, Hyang Mi last_name: Moon - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Liqun full_name: Luo, Liqun last_name: Luo - first_name: Anthony full_name: Wynshaw-Boris, Anthony last_name: Wynshaw-Boris citation: 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 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 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. 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. 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. 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. short: H.M. Moon, S. Hippenmeyer, L. Luo, A. Wynshaw-Boris, ELife 9 (2020). date_created: 2020-03-20T13:16:41Z date_published: 2020-03-11T00:00:00Z date_updated: 2023-08-18T07:06:31Z day: '11' ddc: - '570' department: - _id: SiHi doi: 10.7554/elife.51512 external_id: isi: - '000522835800001' pmid: - '32159512' file: - access_level: open_access checksum: 396ceb2dd10b102ef4e699666b9342c3 content_type: application/pdf creator: dernst date_created: 2020-09-24T07:03:20Z date_updated: 2020-09-24T07:03:20Z file_id: '8567' file_name: 2020_elife_Moon.pdf file_size: 15089438 relation: main_file success: 1 file_date_updated: 2020-09-24T07:03:20Z has_accepted_license: '1' intvolume: ' 9' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/751958 month: '03' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 9 year: '2020' ... --- _id: '8093' 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." 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." article_processing_charge: No article_type: original author: - first_name: Andreas full_name: Hippe, Andreas last_name: Hippe - first_name: Stephan Alexander full_name: Braun, Stephan Alexander last_name: Braun - first_name: Péter full_name: Oláh, Péter last_name: Oláh - first_name: Peter Arne full_name: Gerber, Peter Arne last_name: Gerber - first_name: Anne full_name: Schorr, Anne last_name: Schorr - first_name: Stephan full_name: Seeliger, Stephan last_name: Seeliger - first_name: Stephanie full_name: Holtz, Stephanie last_name: Holtz - first_name: Katharina full_name: Jannasch, Katharina last_name: Jannasch - first_name: Andor full_name: Pivarcsi, Andor last_name: Pivarcsi - first_name: Bettina full_name: Buhren, Bettina last_name: Buhren - first_name: Holger full_name: Schrumpf, Holger last_name: Schrumpf - first_name: Andreas full_name: Kislat, Andreas last_name: Kislat - first_name: Erich full_name: Bünemann, Erich last_name: Bünemann - first_name: Martin full_name: Steinhoff, Martin last_name: Steinhoff - first_name: Jens full_name: Fischer, Jens last_name: Fischer - first_name: Sérgio A. full_name: Lira, Sérgio A. last_name: Lira - first_name: Petra full_name: Boukamp, Petra last_name: Boukamp - first_name: Peter full_name: Hevezi, Peter last_name: Hevezi - first_name: Nikolas Hendrik full_name: Stoecklein, Nikolas Hendrik last_name: Stoecklein - first_name: Thomas full_name: Hoffmann, Thomas last_name: Hoffmann - first_name: Frauke full_name: Alves, Frauke last_name: Alves - first_name: Jonathan full_name: Sleeman, Jonathan last_name: Sleeman - first_name: Thomas full_name: Bauer, Thomas last_name: Bauer - first_name: Jörg full_name: Klufa, Jörg last_name: Klufa - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Maria full_name: Sibilia, Maria last_name: Sibilia - first_name: Albert full_name: Zlotnik, Albert last_name: Zlotnik - first_name: Anja full_name: Müller-Homey, Anja last_name: Müller-Homey - first_name: Bernhard full_name: Homey, Bernhard last_name: Homey citation: 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 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 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. 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. 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. 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. date_created: 2020-07-05T22:00:46Z date_published: 2020-09-15T00:00:00Z date_updated: 2023-08-22T07:51:12Z day: '15' ddc: - '610' department: - _id: SiHi doi: 10.1038/s41416-020-0943-2 external_id: isi: - '000544152500001' pmid: - '32601464' file: - access_level: open_access checksum: 05a8e65d49c3f5b8e37ac4afe68287e2 content_type: application/pdf creator: cchlebak date_created: 2021-12-02T12:35:12Z date_updated: 2021-12-02T12:35:12Z file_id: '10398' file_name: 2020_BrJournalCancer_Hippe.pdf file_size: 3620691 relation: main_file success: 1 file_date_updated: 2021-12-02T12:35:12Z has_accepted_license: '1' intvolume: ' 123' isi: 1 language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: 942-954 pmid: 1 publication: British Journal of Cancer publication_identifier: eissn: - 1532-1827 issn: - 0007-0920 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: erratum url: https://doi.org/10.1038/s41416-021-01563-y record: - id: '10170' relation: later_version status: deleted scopus_import: '1' status: public title: EGFR/Ras-induced CCL20 production modulates the tumour microenvironment tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 123 year: '2020' ... --- _id: '8162' 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. acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: PreCl 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. article_processing_charge: No article_type: original author: - first_name: Susanne full_name: Laukoter, Susanne id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87 last_name: Laukoter orcid: 0000-0002-7903-3010 - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Robert J full_name: Beattie, Robert J id: 2E26DF60-F248-11E8-B48F-1D18A9856A87 last_name: Beattie orcid: 0000-0002-8483-8753 - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Andi H full_name: Hansen, Andi H id: 38853E16-F248-11E8-B48F-1D18A9856A87 last_name: Hansen - first_name: Carmen full_name: Streicher, Carmen id: 36BCB99C-F248-11E8-B48F-1D18A9856A87 last_name: Streicher - first_name: Thomas full_name: Penz, Thomas last_name: Penz - first_name: Christoph full_name: Bock, Christoph last_name: Bock orcid: 0000-0001-6091-3088 - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: 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 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 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. 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. 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. 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. 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. date_created: 2020-07-23T16:03:12Z date_published: 2020-09-23T00:00:00Z date_updated: 2023-08-22T08:20:11Z day: '23' ddc: - '570' department: - _id: SiHi doi: 10.1016/j.neuron.2020.06.031 ec_funded: 1 external_id: isi: - '000579698700006' file: - access_level: open_access checksum: 7becdc16a6317304304631087ae7dd7f content_type: application/pdf creator: dernst date_created: 2020-12-02T09:26:46Z date_updated: 2020-12-02T09:26:46Z file_id: '8828' file_name: 2020_Neuron_Laukoter.pdf file_size: 8911830 relation: main_file success: 1 file_date_updated: 2020-12-02T09:26:46Z has_accepted_license: '1' intvolume: ' 107' isi: 1 issue: '6' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: 1160-1179.e9 project: - _id: 2625A13E-B435-11E9-9278-68D0E5697425 grant_number: '24812' name: Molecular Mechanisms of Radial Neuronal Migration - _id: 268F8446-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: T0101031 name: Role of Eed in neural stem cell lineage progression - _id: 264E56E2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: M02416 name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex - _id: 25D92700-B435-11E9-9278-68D0E5697425 grant_number: LS13-002 name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain - _id: 25D7962E-B435-11E9-9278-68D0E5697425 grant_number: RGP0053/2014 name: Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level - _id: 25D61E48-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618444' name: Molecular Mechanisms of Cerebral Cortex Development - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication: Neuron publication_identifier: issn: - 0896-6273 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on IST Website relation: press_release url: https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/ scopus_import: '1' status: public title: Cell-type specificity of genomic imprinting in cerebral cortex tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 107 year: '2020' ... --- _id: '8592' abstract: - lang: eng 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. 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. article_number: '2001724' article_processing_charge: No article_type: original author: - first_name: Anhao full_name: Tian, Anhao last_name: Tian - first_name: Bo full_name: Kang, Bo last_name: Kang - first_name: Baizhou full_name: Li, Baizhou last_name: Li - first_name: Biying full_name: Qiu, Biying last_name: Qiu - first_name: Wenhong full_name: Jiang, Wenhong last_name: Jiang - first_name: Fangjie full_name: Shao, Fangjie last_name: Shao - first_name: Qingqing full_name: Gao, Qingqing last_name: Gao - first_name: Rui full_name: Liu, Rui last_name: Liu - first_name: Chengwei full_name: Cai, Chengwei last_name: Cai - first_name: Rui full_name: Jing, Rui last_name: Jing - first_name: Wei full_name: Wang, Wei last_name: Wang - first_name: Pengxiang full_name: Chen, Pengxiang last_name: Chen - first_name: Qinghui full_name: Liang, Qinghui last_name: Liang - first_name: Lili full_name: Bao, Lili last_name: Bao - first_name: Jianghong full_name: Man, Jianghong last_name: Man - first_name: Yan full_name: Wang, Yan last_name: Wang - first_name: Yu full_name: Shi, Yu last_name: Shi - first_name: Jin full_name: Li, Jin last_name: Li - first_name: Minmin full_name: Yang, Minmin last_name: Yang - first_name: Lisha full_name: Wang, Lisha last_name: Wang - first_name: Jianmin full_name: Zhang, Jianmin last_name: Zhang - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Junming full_name: Zhu, Junming last_name: Zhu - first_name: Xiuwu full_name: Bian, Xiuwu last_name: Bian - first_name: Ying‐Jie full_name: Wang, Ying‐Jie last_name: Wang - first_name: Chong full_name: Liu, Chong last_name: Liu citation: 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 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 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. 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. 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. 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. 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). date_created: 2020-10-01T09:44:13Z date_published: 2020-11-04T00:00:00Z date_updated: 2023-08-22T09:53:01Z day: '04' ddc: - '570' department: - _id: SiHi doi: 10.1002/advs.202001724 ec_funded: 1 external_id: isi: - '000573860700001' file: - access_level: open_access checksum: 92818c23ecc70e35acfa671f3cfb9909 content_type: application/pdf creator: dernst date_created: 2020-12-10T14:07:24Z date_updated: 2020-12-10T14:07:24Z file_id: '8938' file_name: 2020_AdvScience_Tian.pdf file_size: 7835833 relation: main_file success: 1 file_date_updated: 2020-12-10T14:07:24Z has_accepted_license: '1' intvolume: ' 7' isi: 1 issue: '21' keyword: - General Engineering - General Physics and Astronomy - General Materials Science - Medicine (miscellaneous) - General Chemical Engineering - Biochemistry - Genetics and Molecular Biology (miscellaneous) language: - iso: eng month: '11' oa: 1 oa_version: Published Version project: - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication: Advanced Science publication_identifier: issn: - 2198-3844 publication_status: published publisher: Wiley quality_controlled: '1' status: public title: Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 7 year: '2020' ...