Show simple item record

dc.contributor.authorSmith, Austinen
dc.contributor.authorGuo, Geen
dc.contributor.authorRostovskaya, Mariyaen
dc.contributor.authorClarke, Jamesen
dc.contributor.authorDietmann, Sabineen
dc.contributor.authorMyers, Samen
dc.contributor.authorBertone, Paulen
dc.contributor.authorReik, Wolfen
dc.date.accessioned2017-06-14T08:13:23Z
dc.date.available2017-06-14T08:13:23Z
dc.date.issued2017-08-01en
dc.identifier.issn0950-1991
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/264753
dc.description.abstractMuch attention has focussed on the conversion of human pluripotent stem cells (PSCs) to a more naïve developmental status. Here we provide a method for resetting via transient histone deacetylase inhibition. The protocol is effective across multiple PSC lines and can proceed without karyotype change. Reset cells can be expanded without feeders with a doubling time of around 24 h. WNT inhibition stabilises the resetting process. The transcriptome of reset cells diverges markedly from that of primed PSCs and shares features with human inner cell mass (ICM). Reset cells activate expression of primate-specific transposable elements. DNA methylation is globally reduced to a level equivalent to that in the ICM and is non-random, with gain of methylation at specific loci. Methylation imprints are mostly lost, however. Reset cells can be re-primed to undergo tri-lineage differentiation and germline specification. In female reset cells, appearance of biallelic X-linked gene transcription indicates reactivation of the silenced X chromosome. On reconversion to primed status, $XIST$-induced silencing restores monoallelic gene expression. The facile and robust conversion routine with accompanying data resources will enable widespread utilisation, interrogation, and refinement of candidate naïve cells.
dc.description.sponsorshipThis research is funded by the Medical Research Council of the United Kingdom (MR/P00072X/1) and European Commission Framework 7 (HEALTH-F4-2013-602423, PluriMes), and in part by the UK Regenerative Medicine Platform (MR/L012537/1). WR is supported by the BBSRC (BB/K010867/1), Wellcome Trust (095645/Z/11/Z), EU BLUEPRINT, and EpiGeneSys. The Cambridge Stem Cell Institute receives core funding from the Wellcome Trust and the Medical Research Council. FvM was funded by a Postdoctoral Fellowship from the Swiss National Science Foundation (SNF)/Novartis. SM is funded by a Wellcome Trust PhD Studentship. AS is a Medical Research Council Professor.
dc.publisherThe Company of Biologists
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectpluripotent stem cellsen
dc.subjectdifferentiationen
dc.subjecthuman embryoen
dc.subjectmethylomeen
dc.subjectreprogrammingen
dc.titleEpigenetic resetting of human pluripotencyen
dc.typeArticle
prism.endingPage2763
prism.issueIdentifier15en
prism.publicationDate2017en
prism.publicationNameDevelopmenten
prism.startingPage2748
prism.volume144en
dc.identifier.doi10.17863/CAM.10457
dcterms.dateAccepted2017-06-09en
rioxxterms.versionofrecord10.1242/dev.146811en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-08-01en
dc.contributor.orcidSmith, Austin [0000-0002-3029-4682]
dc.contributor.orcidBertone, Paul [0000-0001-5059-4829]
dc.contributor.orcidReik, Wolf [0000-0003-0216-9881]
dc.identifier.eissn1477-9129
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (097922/Z/11/Z)
pubs.funder-project-idEuropean Commission (602423)
pubs.funder-project-idMRC (MR/P00072X/1)
pubs.funder-project-idMRC (G1001028)
cam.issuedOnline2017-08-01en
cam.orpheus.successThu Jan 30 12:53:46 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

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