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dc.contributor.authorHu, Benxia
dc.contributor.authorWon, Hyejung
dc.contributor.authorMah, Won
dc.contributor.authorPark, Royce B.
dc.contributor.authorKassim, Bibi
dc.contributor.authorSpiess, Keeley
dc.contributor.authorKozlenkov, Alexey
dc.contributor.authorCrowley, Cheynna A.
dc.contributor.authorPochareddy, Sirisha
dc.contributor.authorLi, Yun
dc.contributor.authorDracheva, Stella
dc.contributor.authorSestan, Nenad
dc.contributor.authorAkbarian, Schahram
dc.contributor.authorGeschwind, Daniel H.
dc.contributor.authorPsychENCODE Consortium
dc.contributor.authorMattei, Eugenio
dc.contributor.authorPurcaro, Michael J.
dc.contributor.authorWeng, Zhiping
dc.contributor.authorMoore, Jill E
dc.contributor.authorPratt, Henry E
dc.contributor.authorHuey, Jack
dc.contributor.authorBorrman, Tyler M.
dc.date2022-08-11T08:08:27.000
dc.date.accessioned2022-08-23T15:55:54Z
dc.date.available2022-08-23T15:55:54Z
dc.date.issued2021-06-25
dc.date.submitted2021-08-10
dc.identifier.citation<p>Hu B, Won H, Mah W, Park RB, Kassim B, Spiess K, Kozlenkov A, Crowley CA, Pochareddy S; PsychENCODE Consortium, Li Y, Dracheva S, Sestan N, Akbarian S, Geschwind DH. Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders. Nat Commun. 2021 Jun 25;12(1):3968. doi: 10.1038/s41467-021-24243-0. PMID: 34172755; PMCID: PMC8233376. <a href="https://doi.org/10.1038/s41467-021-24243-0">Link to article on publisher's site</a></p>
dc.identifier.issn2041-1723 (Linking)
dc.identifier.doi10.1038/s41467-021-24243-0
dc.identifier.pmid34172755
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29857
dc.description<p>Eugenio Mattei, Michael Purcaro, Zhiping Weng, Jill Moore, Henry Pratt, Jack Huey, and Tyler Borrman are collaborators in the PsychENCODE Consortium.</p>
dc.description.abstractCellular heterogeneity in the human brain obscures the identification of robust cellular regulatory networks, which is necessary to understand the function of non-coding elements and the impact of non-coding genetic variation. Here we integrate genome-wide chromosome conformation data from purified neurons and glia with transcriptomic and enhancer profiles, to characterize the gene regulatory landscape of two major cell classes in the human brain. We then leverage cell-type-specific regulatory landscapes to gain insight into the cellular etiology of several brain disorders. We find that Alzheimer's disease (AD)-associated epigenetic dysregulation is linked to neurons and oligodendrocytes, whereas genetic risk factors for AD highlighted microglia, suggesting that different cell types may contribute to disease risk, via different mechanisms. Moreover, integration of glutamatergic and GABAergic regulatory maps with genetic risk factors for schizophrenia (SCZ) and bipolar disorder (BD) identifies shared (parvalbumin-expressing interneurons) and distinct cellular etiologies (upper layer neurons for BD, and deeper layer projection neurons for SCZ). Collectively, these findings shed new light on cell-type-specific gene regulatory networks in brain disorders.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=34172755&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectEpigenetics
dc.subjectEpigenomics
dc.subjectChromatin
dc.subjectEpigenetics in the nervous system
dc.subjectGenetics of the nervous system
dc.subjectCell Biology
dc.subjectDevelopmental Neuroscience
dc.subjectMolecular and Cellular Neuroscience
dc.subjectNervous System Diseases
dc.subjectNeurology
dc.subjectPsychiatry
dc.subjectPsychiatry and Psychology
dc.titleNeuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders
dc.typeJournal Article
dc.source.journaltitleNature communications
dc.source.volume12
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3084&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/2065
dc.identifier.contextkey24268199
refterms.dateFOA2022-08-23T15:55:54Z
html.description.abstract<p>Cellular heterogeneity in the human brain obscures the identification of robust cellular regulatory networks, which is necessary to understand the function of non-coding elements and the impact of non-coding genetic variation. Here we integrate genome-wide chromosome conformation data from purified neurons and glia with transcriptomic and enhancer profiles, to characterize the gene regulatory landscape of two major cell classes in the human brain. We then leverage cell-type-specific regulatory landscapes to gain insight into the cellular etiology of several brain disorders. We find that Alzheimer's disease (AD)-associated epigenetic dysregulation is linked to neurons and oligodendrocytes, whereas genetic risk factors for AD highlighted microglia, suggesting that different cell types may contribute to disease risk, via different mechanisms. Moreover, integration of glutamatergic and GABAergic regulatory maps with genetic risk factors for schizophrenia (SCZ) and bipolar disorder (BD) identifies shared (parvalbumin-expressing interneurons) and distinct cellular etiologies (upper layer neurons for BD, and deeper layer projection neurons for SCZ). Collectively, these findings shed new light on cell-type-specific gene regulatory networks in brain disorders.</p>
dc.identifier.submissionpathfaculty_pubs/2065
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentProgram in Bioinformatics and Integrative Biology
dc.source.pages3968


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Copyright © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as Copyright © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.