--- _id: '6995' abstract: - lang: eng 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. 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. alternative_title: - Nature Neuroscience article_processing_charge: Yes author: - first_name: Ranmal A. full_name: Samarasinghe, Ranmal A. last_name: Samarasinghe - first_name: Osvaldo full_name: Miranda, Osvaldo id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425 last_name: Miranda orcid: 0000-0001-6618-6889 - first_name: Jessie E. full_name: Buth, Jessie E. last_name: Buth - first_name: Simon full_name: Mitchell, Simon last_name: Mitchell - first_name: Isabella full_name: Ferando, Isabella last_name: Ferando - first_name: Momoko full_name: Watanabe, Momoko last_name: Watanabe - first_name: Arinnae full_name: Kurdian, Arinnae last_name: Kurdian - first_name: Peyman full_name: Golshani, Peyman last_name: Golshani - first_name: Kathrin full_name: Plath, Kathrin last_name: Plath - first_name: William E. full_name: Lowry, William E. last_name: Lowry - first_name: Jack M. full_name: Parent, Jack M. last_name: Parent - first_name: Istvan full_name: Mody, Istvan last_name: Mody - first_name: Bennett G. full_name: Novitch, Bennett G. last_name: Novitch citation: 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 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 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. ieee: R. A. Samarasinghe et al., Identification of neural oscillations and epileptiform changes in human brain organoids, vol. 24. Springer Nature, 2021. 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. 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. 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. date_created: 2019-11-10T11:23:58Z date_published: 2021-08-23T00:00:00Z date_updated: 2023-08-04T10:49:44Z day: '23' department: - _id: GradSch - _id: SiHi doi: 10.1038/s41593-021-00906-5 external_id: isi: - '000687516300001' pmid: - '34426698 ' intvolume: ' 24' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1038/s41593-021-00906-5 month: '08' oa: 1 oa_version: Published Version page: '32' pmid: 1 publication_identifier: eissn: - 1546-1726 issn: - 1097-6256 publication_status: published publisher: Springer Nature status: public title: Identification of neural oscillations and epileptiform changes in human brain organoids type: technical_report user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 24 year: '2021' ... --- _id: '8546' 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. 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 . article_number: '109208' article_processing_charge: No article_type: original author: - first_name: Tingting full_name: Zhang, Tingting last_name: Zhang - first_name: Tengyuan full_name: Liu, Tengyuan last_name: Liu - first_name: Natalia full_name: Mora, Natalia last_name: Mora - first_name: Justine full_name: Guegan, Justine last_name: Guegan - first_name: Mathilde full_name: Bertrand, Mathilde last_name: Bertrand - first_name: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras - 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: Marica full_name: Anderle, Marica last_name: Anderle - first_name: Natasha full_name: Danda, Natasha last_name: Danda - first_name: Luca full_name: Tiberi, Luca last_name: Tiberi - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Bassem A. full_name: Hassan, Bassem A. last_name: Hassan citation: 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 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. 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. 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. 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. 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). date_created: 2020-09-21T12:00:48Z date_published: 2021-06-08T00:00:00Z date_updated: 2023-08-04T11:00:48Z day: '08' ddc: - '570' department: - _id: SiHi doi: 10.1016/j.celrep.2021.109208 ec_funded: 1 external_id: isi: - '000659894300001' pmid: - '34107249 ' file: - access_level: open_access checksum: 7def3d42ebc8f5675efb6f38819e3e2e content_type: application/pdf creator: cziletti date_created: 2021-06-15T14:01:35Z date_updated: 2021-06-15T14:01:35Z file_id: '9554' file_name: 2021_CellReports_Zhang.pdf file_size: 8900385 relation: main_file success: 1 file_date_updated: 2021-06-15T14:01:35Z has_accepted_license: '1' intvolume: ' 35' isi: 1 issue: '10' language: - iso: eng month: '06' oa: 1 oa_version: Published Version pmid: 1 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: 2625A13E-B435-11E9-9278-68D0E5697425 grant_number: '24812' name: Molecular Mechanisms of Radial Neuronal Migration publication: Cell Reports publication_identifier: eissn: - ' 22111247' publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - relation: earlier_version url: https://doi.org/10.1101/2020.03.18.997205 scopus_import: '1' status: public title: Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum 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: 35 year: '2021' ... --- _id: '9188' abstract: - lang: eng 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. 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. article_number: '104986' article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler - first_name: Quanah full_name: Hudson, Quanah last_name: Hudson - first_name: Susanne full_name: Laukoter, Susanne id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87 last_name: Laukoter - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: 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 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 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. 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. 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. 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. short: F. Pauler, Q. Hudson, S. Laukoter, S. Hippenmeyer, Neurochemistry International 145 (2021). date_created: 2021-02-23T12:31:43Z date_published: 2021-05-01T00:00:00Z date_updated: 2023-08-07T13:48:26Z day: '01' ddc: - '570' department: - _id: SiHi doi: 10.1016/j.neuint.2021.104986 ec_funded: 1 external_id: isi: - '000635575000005' pmid: - '33600873' file: - access_level: open_access checksum: c6d7a40089cd29e289f9b22e75768304 content_type: application/pdf creator: kschuh date_created: 2021-08-11T12:30:38Z date_updated: 2021-08-11T12:30:38Z file_id: '9883' file_name: 2021_NCI_Pauler.pdf file_size: 7083499 relation: main_file success: 1 file_date_updated: 2021-08-11T12:30:38Z has_accepted_license: '1' intvolume: ' 145' isi: 1 issue: '5' keyword: - Cell Biology - Cellular and Molecular Neuroscience language: - iso: eng month: '05' oa: 1 oa_version: Published Version pmid: 1 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: 25D92700-B435-11E9-9278-68D0E5697425 grant_number: LS13-002 name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain publication: Neurochemistry International publication_identifier: issn: - 0197-0186 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond 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: 145 year: '2021' ... --- _id: '9601' abstract: - lang: eng 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.' 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). article_number: '3804' article_processing_charge: No article_type: original author: - first_name: Laura full_name: Santini, Laura last_name: Santini - first_name: Florian full_name: Halbritter, Florian last_name: Halbritter - first_name: Fabian full_name: Titz-Teixeira, Fabian last_name: Titz-Teixeira - first_name: Toru full_name: Suzuki, Toru last_name: Suzuki - first_name: Maki full_name: Asami, Maki last_name: Asami - first_name: Xiaoyan full_name: Ma, Xiaoyan last_name: Ma - first_name: Julia full_name: Ramesmayer, Julia last_name: Ramesmayer - first_name: Andreas full_name: Lackner, Andreas last_name: Lackner - first_name: Nick full_name: Warr, Nick last_name: Warr - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Ernest full_name: Laue, Ernest last_name: Laue - first_name: Matthias full_name: Farlik, Matthias last_name: Farlik - first_name: Christoph full_name: Bock, Christoph last_name: Bock - first_name: Andreas full_name: Beyer, Andreas last_name: Beyer - first_name: Anthony C.F. full_name: Perry, Anthony C.F. last_name: Perry - first_name: Martin full_name: Leeb, Martin last_name: Leeb citation: 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 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. ieee: L. Santini et al., “Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3,” Nature Communications, vol. 12, no. 1. Springer Nature, 2021. 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). date_created: 2021-06-27T22:01:46Z date_published: 2021-07-12T00:00:00Z date_updated: 2023-08-10T13:53:23Z day: '12' ddc: - '570' department: - _id: SiHi doi: 10.1038/s41467-021-23510-4 external_id: isi: - '000667248600005' file: - access_level: open_access checksum: 75dd89d09945185b2d14b2434a0bcb50 content_type: application/pdf creator: asandaue date_created: 2021-06-28T08:04:22Z date_updated: 2021-06-28T08:04:22Z file_id: '9608' file_name: 2021_NatureCommunications_Santini.pdf file_size: 2156554 relation: main_file success: 1 file_date_updated: 2021-06-28T08:04:22Z has_accepted_license: '1' intvolume: ' 12' isi: 1 issue: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version publication: Nature Communications publication_identifier: eissn: - '20411723' publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3 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: 12 year: '2021' ... --- _id: '9603' 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 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. article_number: '109274' article_processing_charge: No article_type: original author: - first_name: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Amarbayasgalan full_name: Davaatseren, Amarbayasgalan id: 70ADC922-B424-11E9-99E3-BA18E6697425 last_name: Davaatseren - first_name: Andi H full_name: Hansen, Andi H id: 38853E16-F248-11E8-B48F-1D18A9856A87 last_name: Hansen - first_name: Johanna full_name: Sonntag, Johanna id: 32FE7D7C-F248-11E8-B48F-1D18A9856A87 last_name: Sonntag - first_name: Lill full_name: Andersen, Lill last_name: Andersen - first_name: Tina full_name: Bernthaler, Tina last_name: Bernthaler - first_name: Carmen full_name: Streicher, Carmen id: 36BCB99C-F248-11E8-B48F-1D18A9856A87 last_name: Streicher - first_name: Anna-Magdalena full_name: Heger, Anna-Magdalena id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87 last_name: Heger - first_name: Randy L. full_name: Johnson, Randy L. last_name: Johnson - first_name: Lindsay A. full_name: Schwarz, Lindsay A. last_name: Schwarz - first_name: Liqun full_name: Luo, Liqun last_name: Luo - first_name: Thomas full_name: Rülicke, Thomas last_name: Rülicke - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: 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 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. 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. 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. 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). date_created: 2021-06-27T22:01:48Z date_published: 2021-06-22T00:00:00Z date_updated: 2023-08-10T13:55:00Z day: '22' ddc: - '570' department: - _id: SiHi - _id: LoSw - _id: PreCl doi: 10.1016/j.celrep.2021.109274 ec_funded: 1 external_id: isi: - '000664463600016' file: - access_level: open_access checksum: d49520fdcbbb5c2f883bddb67cee5d77 content_type: application/pdf creator: asandaue date_created: 2021-06-28T14:06:24Z date_updated: 2021-06-28T14:06:24Z file_id: '9613' file_name: 2021_CellReports_Contreras.pdf file_size: 7653149 relation: main_file success: 1 file_date_updated: 2021-06-28T14:06:24Z has_accepted_license: '1' intvolume: ' 35' isi: 1 issue: '12' language: - iso: eng month: '06' oa: 1 oa_version: Published Version project: - _id: 2625A13E-B435-11E9-9278-68D0E5697425 grant_number: '24812' name: Molecular Mechanisms of Radial Neuronal Migration - _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: Cell Reports publication_identifier: eissn: - '22111247' publication_status: published publisher: Cell Press quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/ scopus_import: '1' status: public title: A genome-wide library of MADM mice for single-cell genetic mosaic analysis 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: 35 year: '2021' ...