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dc.contributor.authorKirschner, Ken
dc.contributor.authorChandra, Ten
dc.contributor.authorKiselev, Ven
dc.contributor.authorFlores-Santa Cruz, Den
dc.contributor.authorMacaulay, ICen
dc.contributor.authorPark, HJen
dc.contributor.authorLi, Juanen
dc.contributor.authorKent, Daviden
dc.contributor.authorKumar, Ren
dc.contributor.authorPask, DCen
dc.contributor.authorHamilton, TLen
dc.contributor.authorHemberg, Men
dc.contributor.authorReik, Wolfen
dc.contributor.authorGreen, Tonyen
dc.date.accessioned2017-07-26T11:07:34Z
dc.date.available2017-07-26T11:07:34Z
dc.date.issued2017-05en
dc.identifier.issn2211-1247
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/265732
dc.description.abstractAging of the hematopoietic stem cell (HSC) compartment is characterized by lineage bias and reduced stem cell function, the molecular basis of which is largely unknown. Using single-cell transcriptomics, we identified a distinct subpopulation of old HSCs carrying a p53 signature indicative of stem cell decline alongside pro-proliferative JAK/STAT signaling. To investigate the relationship between JAK/STAT and p53 signaling, we challenged HSCs with a constitutively active form of JAK2 (V617F) and observed an expansion of the p53-positive subpopulation in old mice. Our results reveal cellular heterogeneity in the onset of HSC aging and implicate a role for JAK2V617F-driven proliferation in the p53-mediated functional decline of old HSCs.
dc.languageengen
dc.language.isoenen
dc.publisherElsevier
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleProliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartmenten
dc.typeArticle
prism.endingPage1511
prism.issueIdentifier8en
prism.publicationDate2017en
prism.publicationNameCell Reportsen
prism.startingPage1503
prism.volume19en
dc.identifier.doi10.17863/CAM.12048
dcterms.dateAccepted2017-04-26en
rioxxterms.versionofrecord10.1016/j.celrep.2017.04.074en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-05en
dc.contributor.orcidKent, David [0000-0001-7871-8811]
dc.contributor.orcidReik, Wolf [0000-0003-0216-9881]
dc.contributor.orcidGreen, Tony [0000-0002-9795-0218]
dc.identifier.eissn2211-1247
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_PC_12009)
pubs.funder-project-idWELLCOME TRUST (104710/Z/14/Z)
cam.issuedOnline2017-05-23en


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