Show simple item record

dc.contributor.authorMoris, Naomi
dc.contributor.authorEdri, Shlomit
dc.contributor.authorSeyres, Denis
dc.contributor.authorKulkarni, Rashmi
dc.contributor.authorDomingues, Ana Filipa
dc.contributor.authorBalayo, Tina
dc.contributor.authorFrontini, Mattia
dc.contributor.authorPina, Cristina
dc.date.accessioned2018-09-27T14:13:08Z
dc.date.available2018-09-27T14:13:08Z
dc.date.issued2018-12
dc.identifier.issn1066-5099
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/282850
dc.description.abstractCell fate transitions in mammalian stem cell systems have often been associated with transcriptional heterogeneity; however, existing data have failed to establish a functional or mechanistic link between the two phenomena. Experiments in unicellular organisms support the notion that transcriptional heterogeneity can be used to facilitate adaptability to environmental changes and have identified conserved chromatin-associated factors that modulate levels of transcriptional noise. Herein, we show destabilization of pluripotency-associated gene regulatory networks through increased transcriptional heterogeneity of mouse embryonic stem cells in which paradigmatic histone acetyl-transferase, and candidate noise modulator, Kat2a (yeast orthologue Gcn5), have been inhibited. Functionally, network destabilization associates with reduced pluripotency and accelerated mesendodermal differentiation, with increased probability of transitions into lineage commitment. Thus, we show evidence of a relationship between transcriptional heterogeneity and cell fate transitions through manipulation of the histone acetylation landscape of mouse embryonic stem cells, suggesting a general principle that could be exploited in other normal and malignant stem cell fate transitions. Stem Cells 2018;36:1828-11.
dc.description.sponsorshipWellcome Trust, BBSRC, Isaac Newton Trust, Kay Kendall Leukaemia Fund, Leuka, British Heart Foundation
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherOxford University Press (OUP)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectPluripotent Stem Cells
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectCell Differentiation
dc.subjectGenetic Heterogeneity
dc.subjectHistone Acetyltransferases
dc.titleHistone Acetyltransferase KAT2A Stabilizes Pluripotency with Control of Transcriptional Heterogeneity.
dc.typeArticle
prism.endingPage1838
prism.issueIdentifier12
prism.publicationDate2018
prism.publicationNameStem Cells
prism.startingPage1828
prism.volume36
dc.identifier.doi10.17863/CAM.30214
dcterms.dateAccepted2018-09-01
rioxxterms.versionofrecord10.1002/stem.2919
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-12
dc.contributor.orcidPina, Cristina [0000-0002-2575-6301]
dc.identifier.eissn1549-4918
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/J014540/1)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idKay Kendall Leukaemia Fund (KKL888)
pubs.funder-project-idIsaac Newton Trust (17.07(f))
pubs.funder-project-idLeuka (unknown)
pubs.funder-project-idBBSRC (1221216)
pubs.funder-project-idEuropean Commission FP7 Network of Excellence (NoE) (282510)
cam.issuedOnline2018-10-17


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International