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dc.contributor.authorFu, Xudong
dc.contributor.authorWu, Xiaoji
dc.contributor.authorDjekidel, Mohamed Nadhir
dc.contributor.authorZhang, Yi
dc.date.accessioned2022-03-29T14:58:18Z
dc.date.issued2019-06-17
dc.identifier.citationFu, Xudong, Wu, Xiaoji, Djekidel, Mohamed Nadhir, and Zhang, Yi. "Myc and Dnmt1 Impede the Pluripotent to Totipotent State Transition in Embryonic Stem Cells." Nature Cell Biology 21, no. 7 (2019): 835-44.en_US
dc.identifier.issn1465-7392en_US
dc.identifier.issn1476-4679en_US
dc.identifier.urihttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37371268*
dc.description.abstractTotipotency refers to the ability of a cell to generate all the cell types of an organism. Unlike pluripotency, the establishment of totipotency is poorly understood. In mouse embryonic stem cells (mESCs), Dux drives a small percentage of cells into a totipotent state by expressing 2-cell-embyro-specific transcripts. To understand how this transition takes place, we performed single cell RNA-seq which revealed a two-step transcriptional reprogramming process characterized by downregulation of pluripotent genes in the first step and upregulation of the 2-cell embryo-specific elements in the second step. To identify factors controlling the transition, we performed a CRISPR/Cas9-mediated screen which revealed Myc and Dnmt1 as two factors preventing the transition. Mechanistic studies demonstrate that Myc prevents down-regulation of pluripotent genes in the first step, while Dnmt1 impedes 2 cell embryo-specific gene activation in the second step. Collectively, our study reveals insights into establishment and regulation of totipotent state in mESCs.en_US
dc.language.isoen_USen_US
dc.publisherSpringer Science and Business Media LLCen_US
dc.relationNature Cell Biologyen_US
dash.licenseLAA
dc.subjectCell Biologyen_US
dc.titleMyc and Dnmt1 Impede the Pluripotent to Totipotent State Transition in Embryonic Stem Cellsen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalNature Cell Biologyen_US
dash.depositing.authorZhang, Yi
dash.waiver2019-04-16
dc.date.available2022-03-29T14:58:18Z
dash.affiliation.otherHarvard Medical Schoolen_US
dc.identifier.doi10.1038/s41556-019-0343-0
dash.waiver.reasonThe open access publishing policy by Harvard is incompatible with Nature publishing group policy.en_US
dash.source.volume21en_US
dash.source.page835-844en_US
dash.source.issue7en_US
dash.contributor.affiliatedDjekidel, Mohamed Nadhir
dash.contributor.affiliatedWu, Xiaoji
dash.contributor.affiliatedFu, Xudong
dash.contributor.affiliatedZhang, Yi


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