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dc.contributor.authorMeyer, Katharina
dc.contributor.authorFeldman, Heather M.
dc.contributor.authorLu, Tao
dc.contributor.authorDrake, Derek
dc.contributor.authorLim, Elaine T.
dc.contributor.authorLing, King-Hwa
dc.contributor.authorBishop, Nicholas A.
dc.contributor.authorPan, Ying
dc.contributor.authorSeo, Jinsoo
dc.contributor.authorLin, Yuan-Ta
dc.contributor.authorSu, Susan C. (Susan Chih-Chieh)
dc.contributor.authorChurch, George M.
dc.contributor.authorTsai, Li-Huei
dc.contributor.authorYankner, Bruce A.
dc.date.accessioned2020-07-27T21:42:04Z
dc.date.available2020-07-27T21:42:04Z
dc.date.issued2019-01
dc.date.submitted2018-12
dc.identifier.issn2211-1247
dc.identifier.urihttps://hdl.handle.net/1721.1/126408
dc.description.abstractThe molecular basis of the earliest neuronal changes that lead to Alzheimer’s disease (AD) is unclear. Here, we analyze neural cells derived from sporadic AD (SAD), APOE4 gene-edited and control induced pluripotent stem cells (iPSCs). We observe major differences in iPSC-derived neural progenitor (NP) cells and neurons in gene networks related to neuronal differentiation, neurogenesis, and synaptic transmission. The iPSC-derived neural cells from SAD patients exhibit accelerated neural differentiation and reduced progenitor cell renewal. Moreover, a similar phenotype appears in NP cells and cerebral organoids derived from APOE4 iPSCs. Impaired function of the transcriptional repressor REST is strongly implicated in the altered transcriptome and differentiation state. SAD and APOE4 expression result in reduced REST nuclear translocation and chromatin binding, and disruption of the nuclear lamina. Thus, dysregulation of neural gene networks may set in motion the pathologic cascade that leads to AD.en_US
dc.description.sponsorshipNational Institutes of Health (Grants R01AG046174, RF1AG048029)en_US
dc.language.isoen
dc.publisherElsevier BVen_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.celrep.2019.01.023en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourceElsevieren_US
dc.titleREST and Neural Gene Network Dysregulation in iPSC Models of Alzheimer’s Diseaseen_US
dc.typeArticleen_US
dc.identifier.citationMeyer, Katharina et al. "REST and Neural Gene Network Dysregulation in iPSC Models of Alzheimer’s Disease." Cell Reports 26, 5 (January 2019): P1112-1127.e9 © 2019 The Author(s)en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentPicower Institute for Learning and Memoryen_US
dc.relation.journalCell Reportsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2019-10-09T12:52:22Z
dspace.date.submission2019-10-09T12:52:29Z
mit.journal.volume26en_US
mit.journal.issue5en_US


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