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dc.contributor.authorLin, Xionghui
dc.contributor.authorSwedlund, Benjamin
dc.contributor.authorTon, Mai-Linh N
dc.contributor.authorGhazanfar, Shila
dc.contributor.authorGuibentif, Carolina
dc.contributor.authorPaulissen, Catherine
dc.contributor.authorBaudelet, Elodie
dc.contributor.authorPlaindoux, Elise
dc.contributor.authorAchouri, Younes
dc.contributor.authorCalonne, Emilie
dc.contributor.authorDubois, Christine
dc.contributor.authorMansfield, William
dc.contributor.authorZaffran, Stéphane
dc.contributor.authorMarioni, John C
dc.contributor.authorFuks, Francois
dc.contributor.authorGöttgens, Berthold
dc.contributor.authorLescroart, Fabienne
dc.contributor.authorBlanpain, Cédric
dc.date.accessioned2022-07-04T23:30:47Z
dc.date.available2022-07-04T23:30:47Z
dc.date.issued2022-07
dc.identifier.issn1465-7392
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338756
dc.description.abstractThe mammalian heart arises from various populations of Mesp1-expressing cardiovascular progenitors (CPs) that are specified during the early stages of gastrulation. Mesp1 is a transcription factor that acts as a master regulator of CP specification and differentiation. However, how Mesp1 regulates the chromatin landscape of nascent mesodermal cells to define the temporal and spatial patterning of the distinct populations of CPs remains unknown. Here, by combining ChIP-seq, RNA-seq and ATAC-seq during mouse pluripotent stem cell differentiation, we defined the dynamic remodelling of the chromatin landscape mediated by Mesp1. We identified different enhancers that are temporally regulated to erase the pluripotent state and specify the pools of CPs that mediate heart development. We identified Zic2 and Zic3 as essential cofactors that act with Mesp1 to regulate its transcription-factor activity at key mesodermal enhancers, thereby regulating the chromatin remodelling and gene expression associated with the specification of the different populations of CPs in vivo. Our study identifies the dynamics of the chromatin landscape and enhancer remodelling associated with temporal patterning of early mesodermal cells into the distinct populations of CPs that mediate heart development.
dc.publisherSpringer Science and Business Media LLC
dc.rightsAll Rights Reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.subjectCambridge Stem Cell Institute
dc.titleMesp1 controls the chromatin and enhancer landscapes essential for spatiotemporal patterning of early cardiovascular progenitors.
dc.typeArticle
dc.publisher.departmentDepartment of Haematology
dc.date.updated2022-07-04T10:39:34Z
prism.publicationNameNat Cell Biol
dc.identifier.doi10.17863/CAM.86166
dcterms.dateAccepted2022-05-25
rioxxterms.versionofrecord10.1038/s41556-022-00947-3
rioxxterms.versionAM
dc.contributor.orcidSwedlund, Benjamin [0000-0002-8264-9342]
dc.contributor.orcidTon, Mai-Linh N [0000-0001-6965-0528]
dc.contributor.orcidGuibentif, Carolina [0000-0003-1056-9922]
dc.contributor.orcidZaffran, Stéphane [0000-0002-0811-418X]
dc.contributor.orcidMarioni, John C [0000-0001-9092-0852]
dc.contributor.orcidFuks, Francois [0000-0003-4637-7287]
dc.contributor.orcidGöttgens, Berthold [0000-0001-6302-5705]
dc.contributor.orcidLescroart, Fabienne [0000-0003-4942-7921]
dc.contributor.orcidBlanpain, Cédric [0000-0002-4028-4322]
dc.identifier.eissn1476-4679
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (203151/Z/16/Z)
cam.issuedOnline2022-07-11
cam.orpheus.successWed Aug 03 09:46:01 BST 2022 - Embargo updated
cam.orpheus.counter1
cam.depositDate2022-07-04
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2023-01-11


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