[{"date_updated":"2023-08-04T10:49:44Z","department":[{"_id":"GradSch"},{"_id":"SiHi"}],"_id":"6995","status":"public","type":"technical_report","language":[{"iso":"eng"}],"publication_identifier":{"issn":["1097-6256"],"eissn":["1546-1726"]},"publication_status":"published","volume":24,"oa_version":"Published Version","pmid":1,"abstract":[{"text":"Human brain organoids represent a powerful tool for the study of human neurological diseases particularly those that impact brain growth and structure. However, many neurological diseases lack obvious anatomical abnormalities, yet significantly impact neural network functions, raising the question of whether organoids possess sufficient neural network architecture and complexity to model these conditions. Here, we explore the network level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex oscillatory network behaviors reminiscent of intact brain preparations. We further demonstrate strikingly abnormal epileptiform network activity in organoids derived from a Rett Syndrome patient despite only modest anatomical differences from isogenically matched controls, and rescue with an unconventional neuromodulatory drug Pifithrin-α. Together, these findings provide an essential foundation for the utilization of human brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery.","lang":"eng"}],"month":"08","intvolume":" 24","alternative_title":["Nature Neuroscience"],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41593-021-00906-5"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Samarasinghe RA, Miranda O, Buth JE, Mitchell S, Ferando I, Watanabe M, Kurdian A, Golshani P, Plath K, Lowry WE, Parent JM, Mody I, Novitch BG. 2021. Identification of neural oscillations and epileptiform changes in human brain organoids, Springer Nature, 32p.","chicago":"Samarasinghe, Ranmal A., Osvaldo Miranda, Jessie E. Buth, Simon Mitchell, Isabella Ferando, Momoko Watanabe, Arinnae Kurdian, et al. Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids. Vol. 24. Springer Nature, 2021. https://doi.org/10.1038/s41593-021-00906-5.","apa":"Samarasinghe, R. A., Miranda, O., Buth, J. E., Mitchell, S., Ferando, I., Watanabe, M., … Novitch, B. G. (2021). Identification of neural oscillations and epileptiform changes in human brain organoids (Vol. 24). Springer Nature. https://doi.org/10.1038/s41593-021-00906-5","ama":"Samarasinghe RA, Miranda O, Buth JE, et al. Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids. Vol 24. Springer Nature; 2021. doi:10.1038/s41593-021-00906-5","ieee":"R. A. Samarasinghe et al., Identification of neural oscillations and epileptiform changes in human brain organoids, vol. 24. Springer Nature, 2021.","short":"R.A. Samarasinghe, O. Miranda, J.E. Buth, S. Mitchell, I. Ferando, M. Watanabe, A. Kurdian, P. Golshani, K. Plath, W.E. Lowry, J.M. Parent, I. Mody, B.G. Novitch, Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids, Springer Nature, 2021.","mla":"Samarasinghe, Ranmal A., et al. Identification of Neural Oscillations and Epileptiform Changes in Human Brain Organoids. Vol. 24, Springer Nature, 2021, doi:10.1038/s41593-021-00906-5."},"title":"Identification of neural oscillations and epileptiform changes in human brain organoids","author":[{"first_name":"Ranmal A.","full_name":"Samarasinghe, Ranmal A.","last_name":"Samarasinghe"},{"first_name":"Osvaldo","id":"862A3C56-A8BF-11E9-B4FA-D9E3E5697425","last_name":"Miranda","full_name":"Miranda, Osvaldo","orcid":"0000-0001-6618-6889"},{"last_name":"Buth","full_name":"Buth, Jessie E.","first_name":"Jessie E."},{"first_name":"Simon","full_name":"Mitchell, Simon","last_name":"Mitchell"},{"first_name":"Isabella","full_name":"Ferando, Isabella","last_name":"Ferando"},{"last_name":"Watanabe","full_name":"Watanabe, Momoko","first_name":"Momoko"},{"first_name":"Arinnae","full_name":"Kurdian, Arinnae","last_name":"Kurdian"},{"first_name":"Peyman","full_name":"Golshani, Peyman","last_name":"Golshani"},{"full_name":"Plath, Kathrin","last_name":"Plath","first_name":"Kathrin"},{"last_name":"Lowry","full_name":"Lowry, William E.","first_name":"William E."},{"full_name":"Parent, Jack M.","last_name":"Parent","first_name":"Jack M."},{"last_name":"Mody","full_name":"Mody, Istvan","first_name":"Istvan"},{"last_name":"Novitch","full_name":"Novitch, Bennett G.","first_name":"Bennett G."}],"article_processing_charge":"Yes","external_id":{"pmid":["34426698 "],"isi":["000687516300001"]},"day":"23","isi":1,"year":"2021","doi":"10.1038/s41593-021-00906-5","date_published":"2021-08-23T00:00:00Z","date_created":"2019-11-10T11:23:58Z","page":"32","acknowledgement":"We thank S. Butler, T. Carmichael and members of the laboratory of B.G.N. for helpful discussions and comments on the manuscript; N. Vishlaghi and F. Turcios-Hernandez for technical assistance, and J. Lee, S.-K. Lee, H. Shinagawa and K. Yoshikawa for valuable reagents. We also thank the UCLA Eli and Edythe Broad Stem Cell Research Center (BSCRC) and Intellectual and Developmental Disabilities Research Center microscopy cores for access to imaging facilities. This work was supported by grants from the California Institute for Regenerative Medicine (CIRM) (DISC1-08819 to B.G.N.), the National Institute of Health (R01NS089817, R01DA051897 and P50HD103557 to B.G.N.; K08NS119747 to R.A.S.; K99HD096105 to M.W.; R01MH123922, R01MH121521 and P50HD103557 to M.J.G.; R01GM099134 to K.P.; R01NS103788 to W.E.L.; R01NS088571 to J.M.P.; R01NS030549 and R01AG050474 to I.M.), and research awards from the UCLA Jonsson Comprehensive Cancer Center and BSCRC Ablon Scholars Program (to B.G.N.), the BSCRC Innovation Program (to B.G.N., K.P. and W.E.L.), the UCLA BSCRC Steffy Brain Aging Research Fund (to B.G.N. and W.E.L.) and the UCLA Clinical and Translational Science Institute (to B.G.N.), Paul Allen Family Foundation Frontiers Group (to K.P. and W.E.L.), the March of Dimes Foundation (to W.E.L.) and the Simons Foundation Autism Research Initiative Bridge to Independence Program (to R.A.S. and M.J.G.). R.A.S. was also supported by the UCLA/NINDS Translational Neuroscience Training Grant (R25NS065723), a Research and Training Fellowship from the American Epilepsy Society, a Taking Flight Award from CURE Epilepsy and a Clinician Scientist training award from the UCLA BSCRC. J.E.B. was supported by the UCLA BSCRC Rose Hills Foundation Graduate Scholarship Training Program. M.W. was supported by postdoctoral training awards provided by the UCLA BSCRC and the Uehara Memorial Foundation. O.A.M. and A.K. were supported in part by the UCLA-California State University Northridge CIRM-Bridges training program (EDUC2-08411). We also acknowledge the support of the IDDRC Cells, Circuits and Systems Analysis, Microscopy and Genetics and Genomics Cores of the Semel Institute of Neuroscience at UCLA, which are supported by the NICHD (U54HD087101 and P50HD10355701). We lastly acknowledge support from a Quantitative and Computational Biosciences Collaboratory Postdoctoral Fellowship to S.M. and the Quantitative and Computational Biosciences Collaboratory community, directed by M. Pellegrini.","publisher":"Springer Nature","oa":1},{"publication_identifier":{"eissn":[" 22111247"]},"publication_status":"published","file":[{"creator":"cziletti","date_updated":"2021-06-15T14:01:35Z","file_size":8900385,"date_created":"2021-06-15T14:01:35Z","file_name":"2021_CellReports_Zhang.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"9554","checksum":"7def3d42ebc8f5675efb6f38819e3e2e","success":1}],"language":[{"iso":"eng"}],"related_material":{"link":[{"url":"https://doi.org/10.1101/2020.03.18.997205","relation":"earlier_version"}]},"volume":35,"issue":"10","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","ec_funded":1,"abstract":[{"lang":"eng","text":"Brain neurons arise from relatively few progenitors generating an enormous diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain neurogenesis is thought to be that excitatory and inhibitory neurons derive from separate, spatially segregated progenitors. Whether bi-potential progenitors with an intrinsic capacity to generate both lineages exist and how such a fate decision may be regulated are unknown. Using cerebellar development as a model, we discover that individual progenitors can give rise to both inhibitory and excitatory lineages. Gradations of Notch activity determine the fates of the progenitors and their daughters. Daughters with the highest levels of Notch activity retain the progenitor fate, while intermediate levels of Notch activity generate inhibitory neurons, and daughters with very low levels of Notch signaling adopt the excitatory fate. Therefore, Notch-mediated binary cell fate choice is a mechanism for regulating the ratio of excitatory to inhibitory neurons from common progenitors."}],"oa_version":"Published Version","pmid":1,"scopus_import":"1","month":"06","intvolume":" 35","date_updated":"2023-08-04T11:00:48Z","ddc":["570"],"file_date_updated":"2021-06-15T14:01:35Z","department":[{"_id":"SiHi"}],"_id":"8546","article_type":"original","type":"journal_article","tmp":{"short":"CC BY-NC-ND (4.0)","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","image":"/images/cc_by_nc_nd.png"},"status":"public","has_accepted_license":"1","isi":1,"year":"2021","day":"08","publication":"Cell Reports","doi":"10.1016/j.celrep.2021.109208","date_published":"2021-06-08T00:00:00Z","date_created":"2020-09-21T12:00:48Z","acknowledgement":"This work was supported by the program “Investissements d’avenir” ANR-10-IAIHU-06 , ICM , a Sorbonne Université Emergence grant, an Allen Distinguished Investigator Award , and the Roger De Spoelberch Foundation Prize (to B.A.H.); Armenise-Harvard Foundation , AIRC , and CARITRO (to L.T.); and the European Research Council under the European Union’s Horizon 2020 research and innovation programme grant agreement no. 725780 LinPro (to S.H.). T.Z. and T.L. were supported by doctoral fellowships from the China Scholarship Council and A.H.H. by a doctoral DOC fellowship of the Austrian Academy of Sciences ( 24812 ). All animal work was conducted at the PHENO-ICMice facility. The Core is supported by 2 “Investissements d’avenir” (ANR-10- IAIHU-06 and ANR-11-INBS-0011-NeurATRIS) and the “Fondation pour la Recherche Médicale.” Light microscopy work was carried out at ICM’s imaging core facility, ICM.Quant, and analysis of scRNA-seq data was carried out at ICM’s bioinformatics core facility, iCONICS. We thank Paulina Ejsmont, Natalia Danda, and Nathalie De Geest for technical support. We are grateful to Dr. Shahragim TAJBAKHSH for providing R26Rstop-NICD-nGFP transgenic mice, Dr. Bart De Strooper for Psn1-deficient mice, Dr. Jean-Christophe Marine for Gt(ROSA)26SortdTom reporter mice, and Dr. Martinez Barbera for Sox2CreERT2 mice. We also give thanks to Dr. Mikio Hoshino for providing Atoh1 and Ptf1a antibodies. B.A.H. is an Einstein Visiting Fellow of the Berlin Institute of Health .","publisher":"Elsevier","quality_controlled":"1","oa":1,"citation":{"mla":"Zhang, Tingting, et al. “Generation of Excitatory and Inhibitory Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” Cell Reports, vol. 35, no. 10, 109208, Elsevier, 2021, doi:10.1016/j.celrep.2021.109208.","ama":"Zhang T, Liu T, Mora N, et al. Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. Cell Reports. 2021;35(10). doi:10.1016/j.celrep.2021.109208","apa":"Zhang, T., Liu, T., Mora, N., Guegan, J., Bertrand, M., Contreras, X., … Hassan, B. A. (2021). Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2021.109208","short":"T. Zhang, T. Liu, N. Mora, J. Guegan, M. Bertrand, X. Contreras, A.H. Hansen, C. Streicher, M. Anderle, N. Danda, L. Tiberi, S. Hippenmeyer, B.A. Hassan, Cell Reports 35 (2021).","ieee":"T. Zhang et al., “Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum,” Cell Reports, vol. 35, no. 10. Elsevier, 2021.","chicago":"Zhang, Tingting, Tengyuan Liu, Natalia Mora, Justine Guegan, Mathilde Bertrand, Ximena Contreras, Andi H Hansen, et al. “Generation of Excitatory and Inhibitory Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” Cell Reports. Elsevier, 2021. https://doi.org/10.1016/j.celrep.2021.109208.","ista":"Zhang T, Liu T, Mora N, Guegan J, Bertrand M, Contreras X, Hansen AH, Streicher C, Anderle M, Danda N, Tiberi L, Hippenmeyer S, Hassan BA. 2021. Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum. Cell Reports. 35(10), 109208."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"first_name":"Tingting","full_name":"Zhang, Tingting","last_name":"Zhang"},{"first_name":"Tengyuan","full_name":"Liu, Tengyuan","last_name":"Liu"},{"last_name":"Mora","full_name":"Mora, Natalia","first_name":"Natalia"},{"first_name":"Justine","full_name":"Guegan, Justine","last_name":"Guegan"},{"last_name":"Bertrand","full_name":"Bertrand, Mathilde","first_name":"Mathilde"},{"first_name":"Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena","last_name":"Contreras"},{"last_name":"Hansen","full_name":"Hansen, Andi H","first_name":"Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Streicher, Carmen","last_name":"Streicher","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen"},{"full_name":"Anderle, Marica","last_name":"Anderle","first_name":"Marica"},{"full_name":"Danda, Natasha","last_name":"Danda","first_name":"Natasha"},{"first_name":"Luca","full_name":"Tiberi, Luca","last_name":"Tiberi"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hassan","full_name":"Hassan, Bassem A.","first_name":"Bassem A."}],"external_id":{"pmid":["34107249 "],"isi":["000659894300001"]},"article_processing_charge":"No","title":"Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum","article_number":"109208","project":[{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"name":"Molecular Mechanisms of Radial Neuronal Migration","grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425"}]},{"scopus_import":"1","month":"05","intvolume":" 145","abstract":[{"text":"Genomic imprinting is an epigenetic mechanism that results in parental allele-specific expression of ~1% of all genes in mouse and human. Imprinted genes are key developmental regulators and play pivotal roles in many biological processes such as nutrient transfer from the mother to offspring and neuronal development. Imprinted genes are also involved in human disease, including neurodevelopmental disorders, and often occur in clusters that are regulated by a common imprint control region (ICR). In extra-embryonic tissues ICRs can act over large distances, with the largest surrounding Igf2r spanning over 10 million base-pairs. Besides classical imprinted expression that shows near exclusive maternal or paternal expression, widespread biased imprinted expression has been identified mainly in brain. In this review we discuss recent developments mapping cell type specific imprinted expression in extra-embryonic tissues and neocortex in the mouse. We highlight the advantages of using an inducible uniparental chromosome disomy (UPD) system to generate cells carrying either two maternal or two paternal copies of a specific chromosome to analyze the functional consequences of genomic imprinting. Mosaic Analysis with Double Markers (MADM) allows fluorescent labeling and concomitant induction of UPD sparsely in specific cell types, and thus to over-express or suppress all imprinted genes on that chromosome. To illustrate the utility of this technique, we explain how MADM-induced UPD revealed new insights about the function of the well-studied Cdkn1c imprinted gene, and how MADM-induced UPDs led to identification of highly cell type specific phenotypes related to perturbed imprinted expression in the mouse neocortex. Finally, we give an outlook on how MADM could be used to probe cell type specific imprinted expression in other tissues in mouse, particularly in extra-embryonic tissues.","lang":"eng"}],"oa_version":"Published Version","pmid":1,"issue":"5","volume":145,"ec_funded":1,"publication_identifier":{"issn":["0197-0186"]},"publication_status":"published","file":[{"creator":"kschuh","date_updated":"2021-08-11T12:30:38Z","file_size":7083499,"date_created":"2021-08-11T12:30:38Z","file_name":"2021_NCI_Pauler.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"c6d7a40089cd29e289f9b22e75768304","file_id":"9883","success":1}],"language":[{"iso":"eng"}],"type":"journal_article","article_type":"original","tmp":{"short":"CC BY-NC-ND (4.0)","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","image":"/images/cc_by_nc_nd.png"},"status":"public","keyword":["Cell Biology","Cellular and Molecular Neuroscience"],"_id":"9188","file_date_updated":"2021-08-11T12:30:38Z","department":[{"_id":"SiHi"}],"date_updated":"2023-08-07T13:48:26Z","ddc":["570"],"quality_controlled":"1","publisher":"Elsevier","oa":1,"acknowledgement":"We thank Melissa Stouffer for critically reading the manuscript. This work was supported by IST Austria institutional funds; NÖ Forschung und Bildung n[f + b] life science call grant (C13-002) 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.","doi":"10.1016/j.neuint.2021.104986","date_published":"2021-05-01T00:00:00Z","date_created":"2021-02-23T12:31:43Z","has_accepted_license":"1","isi":1,"year":"2021","day":"01","publication":"Neurochemistry International","project":[{"grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"},{"grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","_id":"25D92700-B435-11E9-9278-68D0E5697425"}],"article_number":"104986","author":[{"first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","full_name":"Pauler, Florian"},{"first_name":"Quanah","last_name":"Hudson","full_name":"Hudson, Quanah"},{"last_name":"Laukoter","full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","first_name":"Susanne"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"pmid":["33600873"],"isi":["000635575000005"]},"article_processing_charge":"Yes (via OA deal)","title":"Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond","citation":{"ista":"Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. 2021. Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond. Neurochemistry International. 145(5), 104986.","chicago":"Pauler, Florian, Quanah Hudson, Susanne Laukoter, and Simon Hippenmeyer. “Inducible Uniparental Chromosome Disomy to Probe Genomic Imprinting at Single-Cell Level in Brain and Beyond.” Neurochemistry International. Elsevier, 2021. https://doi.org/10.1016/j.neuint.2021.104986.","short":"F. Pauler, Q. Hudson, S. Laukoter, S. Hippenmeyer, Neurochemistry International 145 (2021).","ieee":"F. Pauler, Q. Hudson, S. Laukoter, and S. Hippenmeyer, “Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond,” Neurochemistry International, vol. 145, no. 5. Elsevier, 2021.","apa":"Pauler, F., Hudson, Q., Laukoter, S., & Hippenmeyer, S. (2021). Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond. Neurochemistry International. Elsevier. https://doi.org/10.1016/j.neuint.2021.104986","ama":"Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond. Neurochemistry International. 2021;145(5). doi:10.1016/j.neuint.2021.104986","mla":"Pauler, Florian, et al. “Inducible Uniparental Chromosome Disomy to Probe Genomic Imprinting at Single-Cell Level in Brain and Beyond.” Neurochemistry International, vol. 145, no. 5, 104986, Elsevier, 2021, doi:10.1016/j.neuint.2021.104986."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"year":"2021","has_accepted_license":"1","isi":1,"publication":"Nature Communications","day":"12","date_created":"2021-06-27T22:01:46Z","date_published":"2021-07-12T00:00:00Z","doi":"10.1038/s41467-021-23510-4","acknowledgement":"The authors thank Robert Feil and Anton Wutz for helpful discussions and comments, Samuel Collombet and Peter Fraser for sharing embryo TAD coordinates, and Andy Riddel at the Cambridge Stem Cell Institute and Thomas Sauer at the Max Perutz Laboratories FACS facility for flow-sorting. We thank the team of the Biomedical Sequencing Facility at the CeMM and the Vienna Biocenter Core Facilities (VBCF) for support with next-generation sequencing. We are grateful to animal care teams at the University of Bath and MRC Harwell. A.C.F.P. acknowledges support from the UK Medical Research Council (MR/N000080/1 and MR/N020294/1) and Biotechnology and Biological Sciences Research Council (BB/P009506/1). L.S. is part of the FWF doctoral programme SMICH and supported by an Austrian Academy of Sciences DOC Fellowship. M.L. is funded by a Vienna Research Group for Young Investigators grant (VRG14-006) by the Vienna Science and Technology Fund (WWTF) and by the Austrian Science Fund FWF (I3786 and P31334).","oa":1,"publisher":"Springer Nature","quality_controlled":"1","citation":{"chicago":"Santini, Laura, Florian Halbritter, Fabian Titz-Teixeira, Toru Suzuki, Maki Asami, Xiaoyan Ma, Julia Ramesmayer, et al. “Genomic Imprinting in Mouse Blastocysts Is Predominantly Associated with H3K27me3.” Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23510-4.","ista":"Santini L, Halbritter F, Titz-Teixeira F, Suzuki T, Asami M, Ma X, Ramesmayer J, Lackner A, Warr N, Pauler F, Hippenmeyer S, Laue E, Farlik M, Bock C, Beyer A, Perry ACF, Leeb M. 2021. Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3. Nature Communications. 12(1), 3804.","mla":"Santini, Laura, et al. “Genomic Imprinting in Mouse Blastocysts Is Predominantly Associated with H3K27me3.” Nature Communications, vol. 12, no. 1, 3804, Springer Nature, 2021, doi:10.1038/s41467-021-23510-4.","short":"L. Santini, F. Halbritter, F. Titz-Teixeira, T. Suzuki, M. Asami, X. Ma, J. Ramesmayer, A. Lackner, N. Warr, F. Pauler, S. Hippenmeyer, E. Laue, M. Farlik, C. Bock, A. Beyer, A.C.F. Perry, M. Leeb, Nature Communications 12 (2021).","ieee":"L. Santini et al., “Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3,” Nature Communications, vol. 12, no. 1. Springer Nature, 2021.","ama":"Santini L, Halbritter F, Titz-Teixeira F, et al. Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23510-4","apa":"Santini, L., Halbritter, F., Titz-Teixeira, F., Suzuki, T., Asami, M., Ma, X., … Leeb, M. (2021). Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-23510-4"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"isi":["000667248600005"]},"article_processing_charge":"No","author":[{"full_name":"Santini, Laura","last_name":"Santini","first_name":"Laura"},{"last_name":"Halbritter","full_name":"Halbritter, Florian","first_name":"Florian"},{"last_name":"Titz-Teixeira","full_name":"Titz-Teixeira, Fabian","first_name":"Fabian"},{"last_name":"Suzuki","full_name":"Suzuki, Toru","first_name":"Toru"},{"first_name":"Maki","last_name":"Asami","full_name":"Asami, Maki"},{"full_name":"Ma, Xiaoyan","last_name":"Ma","first_name":"Xiaoyan"},{"first_name":"Julia","last_name":"Ramesmayer","full_name":"Ramesmayer, Julia"},{"first_name":"Andreas","last_name":"Lackner","full_name":"Lackner, Andreas"},{"full_name":"Warr, Nick","last_name":"Warr","first_name":"Nick"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler"},{"first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer"},{"full_name":"Laue, Ernest","last_name":"Laue","first_name":"Ernest"},{"full_name":"Farlik, Matthias","last_name":"Farlik","first_name":"Matthias"},{"first_name":"Christoph","last_name":"Bock","full_name":"Bock, Christoph"},{"first_name":"Andreas","full_name":"Beyer, Andreas","last_name":"Beyer"},{"last_name":"Perry","full_name":"Perry, Anthony C.F.","first_name":"Anthony C.F."},{"first_name":"Martin","last_name":"Leeb","full_name":"Leeb, Martin"}],"title":"Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3","article_number":"3804","publication_status":"published","publication_identifier":{"eissn":["20411723"]},"language":[{"iso":"eng"}],"file":[{"file_name":"2021_NatureCommunications_Santini.pdf","date_created":"2021-06-28T08:04:22Z","creator":"asandaue","file_size":2156554,"date_updated":"2021-06-28T08:04:22Z","success":1,"checksum":"75dd89d09945185b2d14b2434a0bcb50","file_id":"9608","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"license":"https://creativecommons.org/licenses/by/4.0/","volume":12,"issue":"1","abstract":[{"text":"In mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation.","lang":"eng"}],"oa_version":"Published Version","scopus_import":"1","intvolume":" 12","month":"07","date_updated":"2023-08-10T13:53:23Z","ddc":["570"],"file_date_updated":"2021-06-28T08:04:22Z","department":[{"_id":"SiHi"}],"_id":"9601","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","status":"public"},{"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"month":"06","intvolume":" 35","scopus_import":"1","file":[{"success":1,"file_id":"9613","checksum":"d49520fdcbbb5c2f883bddb67cee5d77","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2021_CellReports_Contreras.pdf","date_created":"2021-06-28T14:06:24Z","creator":"asandaue","file_size":7653149,"date_updated":"2021-06-28T14:06:24Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["22111247"]},"publication_status":"published","issue":"12","volume":35,"related_material":{"link":[{"url":"https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/","relation":"press_release","description":"News on IST Homepage"}]},"ec_funded":1,"_id":"9603","status":"public","type":"journal_article","article_type":"original","tmp":{"short":"CC BY-NC-ND (4.0)","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","image":"/images/cc_by_nc_nd.png"},"ddc":["570"],"date_updated":"2023-08-10T13:55:00Z","file_date_updated":"2021-06-28T14:06:24Z","department":[{"_id":"SiHi"},{"_id":"LoSw"},{"_id":"PreCl"}],"acknowledgement":"We thank the Bioimaging, Life Science, and Pre-Clinical Facilities at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain, M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance; R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of the Hippenmeyer lab for discussion. This work was supported by National Institutes of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This work also received support from IST Austria institutional funds , FWF SFB F78 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.","quality_controlled":"1","publisher":"Cell Press","oa":1,"day":"22","publication":"Cell Reports","isi":1,"has_accepted_license":"1","year":"2021","doi":"10.1016/j.celrep.2021.109274","date_published":"2021-06-22T00:00:00Z","date_created":"2021-06-27T22:01:48Z","article_number":"109274","project":[{"name":"Molecular Mechanisms of Radial Neuronal Migration","grant_number":"24812","_id":"2625A13E-B435-11E9-9278-68D0E5697425"},{"_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen, Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” Cell Reports. Cell Press, 2021. https://doi.org/10.1016/j.celrep.2021.109274.","ista":"Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 35(12), 109274.","mla":"Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” Cell Reports, vol. 35, no. 12, 109274, Cell Press, 2021, doi:10.1016/j.celrep.2021.109274.","ama":"Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 2021;35(12). doi:10.1016/j.celrep.2021.109274","apa":"Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen, L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2021.109274","short":"X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen, T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo, T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).","ieee":"X. Contreras et al., “A genome-wide library of MADM mice for single-cell genetic mosaic analysis,” Cell Reports, vol. 35, no. 12. Cell Press, 2021."},"title":"A genome-wide library of MADM mice for single-cell genetic mosaic analysis","author":[{"id":"475990FE-F248-11E8-B48F-1D18A9856A87","first_name":"Ximena","last_name":"Contreras","full_name":"Contreras, Ximena"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","last_name":"Amberg","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207"},{"id":"70ADC922-B424-11E9-99E3-BA18E6697425","first_name":"Amarbayasgalan","last_name":"Davaatseren","full_name":"Davaatseren, Amarbayasgalan"},{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","last_name":"Hansen","full_name":"Hansen, Andi H"},{"first_name":"Johanna","id":"32FE7D7C-F248-11E8-B48F-1D18A9856A87","last_name":"Sonntag","full_name":"Sonntag, Johanna"},{"first_name":"Lill","full_name":"Andersen, Lill","last_name":"Andersen"},{"full_name":"Bernthaler, Tina","last_name":"Bernthaler","first_name":"Tina"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen","last_name":"Streicher","full_name":"Streicher, Carmen"},{"id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","first_name":"Anna-Magdalena","full_name":"Heger, Anna-Magdalena","last_name":"Heger"},{"first_name":"Randy L.","full_name":"Johnson, Randy L.","last_name":"Johnson"},{"last_name":"Schwarz","full_name":"Schwarz, Lindsay A.","first_name":"Lindsay A."},{"first_name":"Liqun","full_name":"Luo, Liqun","last_name":"Luo"},{"first_name":"Thomas","last_name":"Rülicke","full_name":"Rülicke, Thomas"},{"first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","last_name":"Hippenmeyer"}],"article_processing_charge":"No","external_id":{"isi":["000664463600016"]}},{"publication":"International Journal of Molecular Sciences","day":"04","year":"2021","has_accepted_license":"1","isi":1,"date_created":"2021-08-15T22:01:27Z","doi":"10.3390/ijms22168385","date_published":"2021-08-04T00:00:00Z","acknowledgement":"Open access funding provided by Medical University of Vienna. The authors would like to thank all the participants and health professionals involved in the present study. We want to thank our technical assistants Barbara Widmar and Matthias Witzmann-Stern for their diligent work and constant assistance. We would like to thank Simon Hippenmeyer for access to\r\nbioinformatic infrastructure and resources.","oa":1,"publisher":"MDPI","quality_controlled":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"apa":"Yotova, I., Hudson, Q. J., Pauler, F., Proestling, K., Haslinger, I., Kuessel, L., … Wenzl, R. (2021). LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms22168385","ama":"Yotova I, Hudson QJ, Pauler F, et al. LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line. International Journal of Molecular Sciences. 2021;22(16). doi:10.3390/ijms22168385","ieee":"I. Yotova et al., “LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line,” International Journal of Molecular Sciences, vol. 22, no. 16. MDPI, 2021.","short":"I. Yotova, Q.J. Hudson, F. Pauler, K. Proestling, I. Haslinger, L. Kuessel, A. Perricos, H. Husslein, R. Wenzl, International Journal of Molecular Sciences 22 (2021).","mla":"Yotova, Iveta, et al. “LINC01133 Inhibits Invasion and Promotes Proliferation in an Endometriosis Epithelial Cell Line.” International Journal of Molecular Sciences, vol. 22, no. 16, 8385, MDPI, 2021, doi:10.3390/ijms22168385.","ista":"Yotova I, Hudson QJ, Pauler F, Proestling K, Haslinger I, Kuessel L, Perricos A, Husslein H, Wenzl R. 2021. LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line. International Journal of Molecular Sciences. 22(16), 8385.","chicago":"Yotova, Iveta, Quanah J. Hudson, Florian Pauler, Katharina Proestling, Isabella Haslinger, Lorenz Kuessel, Alexandra Perricos, Heinrich Husslein, and René Wenzl. “LINC01133 Inhibits Invasion and Promotes Proliferation in an Endometriosis Epithelial Cell Line.” International Journal of Molecular Sciences. MDPI, 2021. https://doi.org/10.3390/ijms22168385."},"title":"LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line","external_id":{"isi":["000689147400001"]},"article_processing_charge":"Yes","author":[{"last_name":"Yotova","full_name":"Yotova, Iveta","first_name":"Iveta"},{"first_name":"Quanah J.","full_name":"Hudson, Quanah J.","last_name":"Hudson"},{"first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048"},{"first_name":"Katharina","full_name":"Proestling, Katharina","last_name":"Proestling"},{"last_name":"Haslinger","full_name":"Haslinger, Isabella","first_name":"Isabella"},{"last_name":"Kuessel","full_name":"Kuessel, Lorenz","first_name":"Lorenz"},{"first_name":"Alexandra","full_name":"Perricos, Alexandra","last_name":"Perricos"},{"last_name":"Husslein","full_name":"Husslein, Heinrich","first_name":"Heinrich"},{"first_name":"René","full_name":"Wenzl, René","last_name":"Wenzl"}],"article_number":"8385","language":[{"iso":"eng"}],"file":[{"success":1,"file_id":"9922","checksum":"be7f0042607ca60549cb27513c19c6af","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2021_InternationalJournalOfMolecularSciences_Yotova.pdf","date_created":"2021-08-16T09:29:17Z","file_size":2646018,"date_updated":"2021-08-16T09:29:17Z","creator":"asandaue"}],"publication_status":"published","publication_identifier":{"issn":["16616596"],"eissn":["14220067"]},"volume":22,"issue":"16","oa_version":"Published Version","abstract":[{"text":"Endometriosis is a common gynecological disorder characterized by ectopic growth of endometrium outside the uterus and is associated with chronic pain and infertility. We investigated the role of the long intergenic noncoding RNA 01133 (LINC01133) in endometriosis, an lncRNA that has been implicated in several types of cancer. We found that LINC01133 is upregulated in ectopic endometriotic lesions. As expression appeared higher in the epithelial endometrial layer, we performed a siRNA knockdown of LINC01133 in an endometriosis epithelial cell line. Phenotypic assays indicated that LINC01133 may promote proliferation and suppress cellular migration, and affect the cytoskeleton and morphology of the cells. Gene ontology analysis of differentially expressed genes indicated that cell proliferation and migration pathways were affected in line with the observed phenotype. We validated upregulation of p21 and downregulation of Cyclin A at the protein level, which together with the quantification of the DNA content using fluorescence-activated cell sorting (FACS) analysis indicated that the observed effects on cellular proliferation may be due to changes in cell cycle. Further, we found testis-specific protein kinase 1 (TESK1) kinase upregulation corresponding with phosphorylation and inactivation of actin severing protein Cofilin, which could explain changes in the cytoskeleton and cellular migration. These results indicate that endometriosis is associated with LINC01133 upregulation, which may affect pathogenesis via the cellular proliferation and migration pathways.","lang":"eng"}],"intvolume":" 22","month":"08","scopus_import":"1","ddc":["570"],"date_updated":"2023-08-11T10:34:13Z","department":[{"_id":"SiHi"}],"file_date_updated":"2021-08-16T09:29:17Z","_id":"9906","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original"},{"ddc":["570"],"date_updated":"2023-09-05T14:03:17Z","department":[{"_id":"SiHi"}],"file_date_updated":"2022-05-27T06:59:55Z","_id":"9073","status":"public","keyword":["General Neuroscience"],"article_type":"original","type":"journal_article","file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"file_id":"11414","checksum":"578fd7ed1a0aef74bce61bea2d987b33","creator":"dernst","file_size":1031150,"date_updated":"2022-05-27T06:59:55Z","file_name":"2021_JourNeuroscience_Hanganu.pdf","date_created":"2022-05-27T06:59:55Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1529-2401"],"issn":["0270-6474"]},"publication_status":"published","volume":41,"issue":"5","ec_funded":1,"oa_version":"Published Version","pmid":1,"abstract":[{"lang":"eng","text":"The sensory and cognitive abilities of the mammalian neocortex are underpinned by intricate columnar and laminar circuits formed from an array of diverse neuronal populations. One approach to determining how interactions between these circuit components give rise to complex behavior is to investigate the rules by which cortical circuits are formed and acquire functionality during development. This review summarizes recent research on the development of the neocortex, from genetic determination in neural stem cells through to the dynamic role that specific neuronal populations play in the earliest circuits of neocortex, and how they contribute to emergent function and cognition. While many of these endeavors take advantage of model systems, consideration will also be given to advances in our understanding of activity in nascent human circuits. Such cross-species perspective is imperative when investigating the mechanisms underlying the dysfunction of early neocortical circuits in neurodevelopmental disorders, so that one can identify targets amenable to therapeutic intervention."}],"month":"02","intvolume":" 41","scopus_import":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Hanganu-Opatz, Ileana L., Simon J. B. Butt, Simon Hippenmeyer, Natalia V. De Marco García, Jessica A. Cardin, Bradley Voytek, and Alysson R. Muotri. “The Logic of Developing Neocortical Circuits in Health and Disease.” The Journal of Neuroscience. Society for Neuroscience, 2021. https://doi.org/10.1523/jneurosci.1655-20.2020.","ista":"Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, De Marco García NV, Cardin JA, Voytek B, Muotri AR. 2021. The logic of developing neocortical circuits in health and disease. The Journal of Neuroscience. 41(5), 813–822.","mla":"Hanganu-Opatz, Ileana L., et al. “The Logic of Developing Neocortical Circuits in Health and Disease.” The Journal of Neuroscience, vol. 41, no. 5, Society for Neuroscience, 2021, pp. 813–22, doi:10.1523/jneurosci.1655-20.2020.","short":"I.L. Hanganu-Opatz, S.J.B. Butt, S. Hippenmeyer, N.V. De Marco García, J.A. Cardin, B. Voytek, A.R. Muotri, The Journal of Neuroscience 41 (2021) 813–822.","ieee":"I. L. Hanganu-Opatz et al., “The logic of developing neocortical circuits in health and disease,” The Journal of Neuroscience, vol. 41, no. 5. Society for Neuroscience, pp. 813–822, 2021.","apa":"Hanganu-Opatz, I. L., Butt, S. J. B., Hippenmeyer, S., De Marco García, N. V., Cardin, J. A., Voytek, B., & Muotri, A. R. (2021). The logic of developing neocortical circuits in health and disease. The Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/jneurosci.1655-20.2020","ama":"Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, et al. The logic of developing neocortical circuits in health and disease. The Journal of Neuroscience. 2021;41(5):813-822. doi:10.1523/jneurosci.1655-20.2020"},"title":"The logic of developing neocortical circuits in health and disease","author":[{"first_name":"Ileana L.","last_name":"Hanganu-Opatz","full_name":"Hanganu-Opatz, Ileana L."},{"first_name":"Simon J. B.","full_name":"Butt, Simon J. B.","last_name":"Butt"},{"first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"},{"first_name":"Natalia V.","last_name":"De Marco García","full_name":"De Marco García, Natalia V."},{"first_name":"Jessica A.","last_name":"Cardin","full_name":"Cardin, Jessica A."},{"full_name":"Voytek, Bradley","last_name":"Voytek","first_name":"Bradley"},{"last_name":"Muotri","full_name":"Muotri, Alysson R.","first_name":"Alysson R."}],"article_processing_charge":"No","external_id":{"pmid":["33431633"],"isi":["000616763400002"]},"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"},{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F07805"}],"day":"03","publication":"The Journal of Neuroscience","isi":1,"has_accepted_license":"1","year":"2021","doi":"10.1523/jneurosci.1655-20.2020","date_published":"2021-02-03T00:00:00Z","date_created":"2021-02-03T12:23:51Z","page":"813-822","acknowledgement":"Work in the I.L.H.-O. laboratory was supported by European Research Council Grant ERC-2015-CoG 681577 and German Research Foundation Ha 4466/10-1, Ha4466/11-1, Ha4466/12-1, SPP 1665, and SFB 936B5. Work in the S.J.B.B. laboratory was supported by Biotechnology and Biological Sciences Research Council BB/P003796/1, Medical Research Council MR/K004387/1 and MR/T033320/1, Wellcome Trust 215199/Z/19/Z and 102386/Z/13/Z, and John Fell Fund. Work in the S.H. laboratory was supported by European Research Council Grants ERC-2016-CoG 725780 LinPro and FWF SFB F78. This work was supported by National Institutes of Health Grant NIMH 1R01MH110553 to N.V.D.M.G. Work in the J.A.C. laboratory was supported by the Ludwig Family Foundation, Simons Foundation SFARI Research Award, and National Institutes of Health/National Institute of Mental Health R01 MH102365 and R01MH113852. The B.V. laboratory was supported by Whitehall Foundation 2017-12-73, National Science Foundation 1736028, National Institutes of Health, National Institute of General Medical Sciences R01GM134363-01, and Halıcıoğlu Data Science Institute Fellowship. This work was supported by the University of California San Diego School of Medicine.","quality_controlled":"1","publisher":"Society for Neuroscience","oa":1},{"date_updated":"2023-09-27T07:46:09Z","department":[{"_id":"SiHi"}],"_id":"9793","type":"journal_article","article_type":"original","status":"public","publication_identifier":{"issn":["0896-6273"],"eissn":["1097-4199"]},"publication_status":"published","language":[{"iso":"eng"}],"volume":109,"issue":"15","ec_funded":1,"abstract":[{"text":"Astrocytes extensively infiltrate the neuropil to regulate critical aspects of synaptic development and function. This process is regulated by transcellular interactions between astrocytes and neurons via cell adhesion molecules. How astrocytes coordinate developmental processes among one another to parse out the synaptic neuropil and form non-overlapping territories is unknown. Here we identify a molecular mechanism regulating astrocyte-astrocyte interactions during development to coordinate astrocyte morphogenesis and gap junction coupling. We show that hepaCAM, a disease-linked, astrocyte-enriched cell adhesion molecule, regulates astrocyte competition for territory and morphological complexity in the developing mouse cortex. Furthermore, conditional deletion of Hepacam from developing astrocytes significantly impairs gap junction coupling between astrocytes and disrupts the balance between synaptic excitation and inhibition. Mutations in HEPACAM cause megalencephalic leukoencephalopathy with subcortical cysts in humans. Therefore, our findings suggest that disruption of astrocyte self-organization mechanisms could be an underlying cause of neural pathology.","lang":"eng"}],"pmid":1,"oa_version":"Published Version","scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.neuron.2021.05.025"}],"month":"08","intvolume":" 109","citation":{"chicago":"Baldwin, Katherine T., Christabel X. Tan, Samuel T. Strader, Changyu Jiang, Justin T. Savage, Xabier Elorza-Vidal, Ximena Contreras, et al. “HepaCAM Controls Astrocyte Self-Organization and Coupling.” Neuron. Elsevier, 2021. https://doi.org/10.1016/j.neuron.2021.05.025.","ista":"Baldwin KT, Tan CX, Strader ST, Jiang C, Savage JT, Elorza-Vidal X, Contreras X, Rülicke T, Hippenmeyer S, Estévez R, Ji R-R, Eroglu C. 2021. HepaCAM controls astrocyte self-organization and coupling. Neuron. 109(15), 2427–2442.e10.","mla":"Baldwin, Katherine T., et al. “HepaCAM Controls Astrocyte Self-Organization and Coupling.” Neuron, vol. 109, no. 15, Elsevier, 2021, p. 2427–2442.e10, doi:10.1016/j.neuron.2021.05.025.","apa":"Baldwin, K. T., Tan, C. X., Strader, S. T., Jiang, C., Savage, J. T., Elorza-Vidal, X., … Eroglu, C. (2021). HepaCAM controls astrocyte self-organization and coupling. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2021.05.025","ama":"Baldwin KT, Tan CX, Strader ST, et al. HepaCAM controls astrocyte self-organization and coupling. Neuron. 2021;109(15):2427-2442.e10. doi:10.1016/j.neuron.2021.05.025","short":"K.T. Baldwin, C.X. Tan, S.T. Strader, C. Jiang, J.T. Savage, X. Elorza-Vidal, X. Contreras, T. Rülicke, S. Hippenmeyer, R. Estévez, R.-R. Ji, C. Eroglu, Neuron 109 (2021) 2427–2442.e10.","ieee":"K. T. Baldwin et al., “HepaCAM controls astrocyte self-organization and coupling,” Neuron, vol. 109, no. 15. Elsevier, p. 2427–2442.e10, 2021."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Katherine T.","last_name":"Baldwin","full_name":"Baldwin, Katherine T."},{"first_name":"Christabel X.","full_name":"Tan, Christabel X.","last_name":"Tan"},{"first_name":"Samuel T.","last_name":"Strader","full_name":"Strader, Samuel T."},{"first_name":"Changyu","last_name":"Jiang","full_name":"Jiang, Changyu"},{"last_name":"Savage","full_name":"Savage, Justin T.","first_name":"Justin T."},{"first_name":"Xabier","last_name":"Elorza-Vidal","full_name":"Elorza-Vidal, Xabier"},{"full_name":"Contreras, Ximena","last_name":"Contreras","id":"475990FE-F248-11E8-B48F-1D18A9856A87","first_name":"Ximena"},{"first_name":"Thomas","last_name":"Rülicke","full_name":"Rülicke, Thomas"},{"first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"},{"full_name":"Estévez, Raúl","last_name":"Estévez","first_name":"Raúl"},{"first_name":"Ru-Rong","full_name":"Ji, Ru-Rong","last_name":"Ji"},{"first_name":"Cagla","last_name":"Eroglu","full_name":"Eroglu, Cagla"}],"article_processing_charge":"No","external_id":{"isi":["000692851900010"],"pmid":["34171291"]},"title":"HepaCAM controls astrocyte self-organization and coupling","project":[{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"isi":1,"year":"2021","day":"04","publication":"Neuron","page":"2427-2442.e10","doi":"10.1016/j.neuron.2021.05.025","date_published":"2021-08-04T00:00:00Z","date_created":"2021-08-06T09:08:25Z","acknowledgement":"This work was supported by the National Institutes of Health (R01 DA047258 and R01 NS102237 to C.E., F32 NS100392 to K.T.B.) and the Holland-Trice Brain Research Award (to C.E.). K.T.B. was supported by postdoctoral fellowships from the Foerster-Bernstein Family and The Hartwell Foundation. The Hippenmeyer lab was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovations program (725780 LinPro) to S.H. R.E. was supported by Ministerio de Ciencia y Tecnología (RTI2018-093493-B-I00). We thank the Duke Light Microscopy Core Facility, the Duke Transgenic Mouse Facility, Dr. U. Schulte for assistance with proteomic experiments, and Dr. D. Silver for critical review of the manuscript. Cartoon elements of figure panels were created using BioRender.com.","quality_controlled":"1","publisher":"Elsevier","oa":1},{"volume":23,"ec_funded":1,"file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"checksum":"77dc540e8011c5475031bdf6ccef20a6","file_id":"10657","creator":"cchlebak","file_size":4794147,"date_updated":"2022-01-24T07:43:09Z","file_name":"2021_MolTherMethodsClinDev_Maes.pdf","date_created":"2022-01-24T07:43:09Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2329-0501"]},"publication_status":"published","month":"12","intvolume":" 23","scopus_import":"1","oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"abstract":[{"text":"Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells, allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy, likely due to the cells’ heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E, R576Q, K493S, and K459S), resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette for use in combination with the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency.\r\n","lang":"eng"}],"file_date_updated":"2022-01-24T07:43:09Z","department":[{"_id":"SaSi"},{"_id":"SiHi"}],"ddc":["570"],"date_updated":"2023-11-16T13:12:03Z","status":"public","article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"10655","date_published":"2021-12-10T00:00:00Z","doi":"10.1016/j.omtm.2021.09.006","date_created":"2022-01-23T23:01:28Z","page":"210-224","day":"10","publication":"Molecular Therapy - Methods and Clinical Development","has_accepted_license":"1","isi":1,"year":"2021","quality_controlled":"1","publisher":"Elsevier","oa":1,"acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 715571). The research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility, the Life Science Facility, and the Pre-Clinical Facility, namely Sonja Haslinger and Michael Schunn for their animal colony management and support. We would also like to thank Chakrabarty Lab for sharing the plasmids for AAV2/6 production. Finally, we would like to thank the Siegert team members for discussion about the manuscript.","title":"Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment","author":[{"orcid":"0000-0001-9642-1085","full_name":"Maes, Margaret E","last_name":"Maes","first_name":"Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Wögenstein","full_name":"Wögenstein, Gabriele M.","first_name":"Gabriele M."},{"id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","first_name":"Gloria","orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria","last_name":"Colombo"},{"orcid":"0000-0001-8293-4568","full_name":"Casado Polanco, Raquel","last_name":"Casado Polanco","id":"15240fc1-dbcd-11ea-9d1d-ac5a786425fd","first_name":"Raquel"},{"first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","last_name":"Siegert"}],"external_id":{"isi":["000748748500019"]},"article_processing_charge":"Yes","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. 2021. Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. Molecular Therapy - Methods and Clinical Development. 23, 210–224.","chicago":"Maes, Margaret E, Gabriele M. Wögenstein, Gloria Colombo, Raquel Casado Polanco, and Sandra Siegert. “Optimizing AAV2/6 Microglial Targeting Identified Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular Therapy - Methods and Clinical Development. Elsevier, 2021. https://doi.org/10.1016/j.omtm.2021.09.006.","ieee":"M. E. Maes, G. M. Wögenstein, G. Colombo, R. Casado Polanco, and S. Siegert, “Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment,” Molecular Therapy - Methods and Clinical Development, vol. 23. Elsevier, pp. 210–224, 2021.","short":"M.E. Maes, G.M. Wögenstein, G. Colombo, R. Casado Polanco, S. Siegert, Molecular Therapy - Methods and Clinical Development 23 (2021) 210–224.","apa":"Maes, M. E., Wögenstein, G. M., Colombo, G., Casado Polanco, R., & Siegert, S. (2021). Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. Molecular Therapy - Methods and Clinical Development. Elsevier. https://doi.org/10.1016/j.omtm.2021.09.006","ama":"Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. Molecular Therapy - Methods and Clinical Development. 2021;23:210-224. doi:10.1016/j.omtm.2021.09.006","mla":"Maes, Margaret E., et al. “Optimizing AAV2/6 Microglial Targeting Identified Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular Therapy - Methods and Clinical Development, vol. 23, Elsevier, 2021, pp. 210–24, doi:10.1016/j.omtm.2021.09.006."},"project":[{"_id":"25D4A630-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715571","name":"Microglia action towards neuronal circuit formation and function in health and disease"}]},{"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","_id":"10321","department":[{"_id":"SiHi"}],"file_date_updated":"2021-11-22T08:23:58Z","ddc":["573"],"date_updated":"2023-11-16T13:08:03Z","intvolume":" 2","month":"11","scopus_import":"1","oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"abstract":[{"text":"Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice. MADM enables concomitant fluorescent cell labeling and introduction of a mutation of a gene of interest with single-cell resolution. This protocol highlights major steps for the generation of genetic mosaic tissue and the isolation and processing of respective tissues for downstream histological analysis. For complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).","lang":"eng"}],"ec_funded":1,"volume":2,"issue":"4","language":[{"iso":"eng"}],"file":[{"date_created":"2021-11-22T08:23:58Z","file_name":"2021_STARProtocols_Amberg.pdf","creator":"cchlebak","date_updated":"2021-11-22T08:23:58Z","file_size":7309464,"checksum":"9e3f6d06bf583e7a8b6a9e9a60500a28","file_id":"10329","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"publication_status":"published","publication_identifier":{"eissn":["2666-1667"]},"project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"},{"_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Role of Eed in neural stem cell lineage progression","grant_number":"T0101031"},{"name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F07805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"}],"article_number":"100939","title":"Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers","article_processing_charge":"Yes","author":[{"full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Amberg N, Hippenmeyer S. 2021. Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers. STAR Protocols. 2(4), 100939.","chicago":"Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate Genes in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols. Cell Press, 2021. https://doi.org/10.1016/j.xpro.2021.100939.","apa":"Amberg, N., & Hippenmeyer, S. (2021). Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers. STAR Protocols. Cell Press. https://doi.org/10.1016/j.xpro.2021.100939","ama":"Amberg N, Hippenmeyer S. Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers. STAR Protocols. 2021;2(4). doi:10.1016/j.xpro.2021.100939","ieee":"N. Amberg and S. Hippenmeyer, “Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers,” STAR Protocols, vol. 2, no. 4. Cell Press, 2021.","short":"N. Amberg, S. Hippenmeyer, STAR Protocols 2 (2021).","mla":"Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate Genes in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols, vol. 2, no. 4, 100939, Cell Press, 2021, doi:10.1016/j.xpro.2021.100939."},"oa":1,"quality_controlled":"1","publisher":"Cell Press","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). We particularly thank Mohammad Goudarzi for assistance with photography of mouse perfusion and dissection. N.A. received support from FWF Firnberg-Programm (T 1031). This work was also supported by IST Austria institutional funds; FWF SFB F78 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.","date_created":"2021-11-21T23:01:28Z","date_published":"2021-11-10T00:00:00Z","doi":"10.1016/j.xpro.2021.100939","publication":"STAR Protocols","day":"10","year":"2021","has_accepted_license":"1"}]