Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice

Cited 293 time in webofscience Cited 255 time in scopus
  • Hit : 348
  • Download : 160
DC FieldValueLanguage
dc.contributor.authorAdam, Rene C.ko
dc.contributor.authorYang, Hanseulko
dc.contributor.authorRockowitz, Shirako
dc.contributor.authorLarsen, Samantha B.ko
dc.contributor.authorNikolova, Mariako
dc.contributor.authorOristian, Daniel S.ko
dc.contributor.authorPolak, Lisako
dc.contributor.authorKadaja, Meelisko
dc.contributor.authorAsare, Ammako
dc.contributor.authorZheng, Deyouko
dc.contributor.authorFuchs, Elaineko
dc.date.accessioned2020-11-17T02:55:15Z-
dc.date.available2020-11-17T02:55:15Z-
dc.date.created2020-11-17-
dc.date.created2020-11-17-
dc.date.issued2015-05-
dc.identifier.citationNATURE, v.521, no.7552, pp.366 - +-
dc.identifier.issn0028-0836-
dc.identifier.urihttp://hdl.handle.net/10203/277329-
dc.description.abstractAdult stem cells occur in niches that balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, stem cells outside their niche often display fate flexibility(1-4). Here we show that super-enhancers(5) underlie the identity, lineage commitment and plasticity of adult stem cells in vivo. Using hair follicle as a model, we map the global chromatin domains of hair follicle stem cells and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters ('epicentres') of transcription factor binding sites undergo remodelling upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicentres, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, hair follicle stem cells dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicentres, enabling their genes to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of hair follicle stem cell super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense transcription-factor-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status but also stemness, plasticity in transitional states and differentiation.-
dc.languageEnglish-
dc.publisherNATURE PUBLISHING GROUP-
dc.titlePioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice-
dc.typeArticle-
dc.identifier.wosid000354816500059-
dc.identifier.scopusid2-s2.0-84929211885-
dc.type.rimsART-
dc.citation.volume521-
dc.citation.issue7552-
dc.citation.beginningpage366-
dc.citation.endingpage+-
dc.citation.publicationnameNATURE-
dc.identifier.doi10.1038/nature14289-
dc.contributor.localauthorYang, Hanseul-
dc.contributor.nonIdAuthorAdam, Rene C.-
dc.contributor.nonIdAuthorRockowitz, Shira-
dc.contributor.nonIdAuthorLarsen, Samantha B.-
dc.contributor.nonIdAuthorNikolova, Maria-
dc.contributor.nonIdAuthorOristian, Daniel S.-
dc.contributor.nonIdAuthorPolak, Lisa-
dc.contributor.nonIdAuthorKadaja, Meelis-
dc.contributor.nonIdAuthorAsare, Amma-
dc.contributor.nonIdAuthorZheng, Deyou-
dc.contributor.nonIdAuthorFuchs, Elaine-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusIDENTITY GENES-
dc.subject.keywordPlusSELF-RENEWAL-
dc.subject.keywordPlusNICHE-
dc.subject.keywordPlusSKIN-
dc.subject.keywordPlusGENOME-
dc.subject.keywordPlusDIFFERENTIATION-
dc.subject.keywordPlusREGENERATION-
dc.subject.keywordPlusINHIBITION-
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 293 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0