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dc.contributor.authorHérault, Aen
dc.contributor.authorBinnewies, Men
dc.contributor.authorLeong, Sen
dc.contributor.authorCalero-Nieto, FJen
dc.contributor.authorZhang, SYen
dc.contributor.authorKang, Y-Aen
dc.contributor.authorWang, Xiaonanen
dc.contributor.authorPietras, EMen
dc.contributor.authorChu, SHen
dc.contributor.authorBarry-Holson, Ken
dc.contributor.authorArmstrong, Sen
dc.contributor.authorGottgens, Bertholden
dc.contributor.authorPassegué, Een
dc.date.accessioned2017-05-02T13:55:56Z
dc.date.available2017-05-02T13:55:56Z
dc.date.issued2017-04-06en
dc.identifier.issn0028-0836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/263950
dc.description.abstractAlthough many aspects of blood production are well understood, the spatial organization of myeloid differentiation in the bone marrow remains unknown. Here we use imaging to track granulocyte/macrophage progenitor (GMP) behaviour in mice during emergency and leukaemic myelopoiesis. In the steady state, we find individual GMPs scattered throughout the bone marrow. During regeneration, we observe expanding GMP patches forming defined GMP clusters, which, in turn, locally differentiate into granulocytes. The timed release of important bone marrow niche signals (SCF, IL-1β, G-CSF, TGFβ and CXCL4) and activation of an inducible $\textit{Irf8}$ and β-catenin progenitor self-renewal network control the transient formation of regenerating GMP clusters. In leukaemia, we show that GMP clusters are constantly produced owing to persistent activation of the self-renewal network and a lack of termination cytokines that normally restore haematopoietic stem-cell quiescence. Our results uncover a previously unrecognized dynamic behaviour of GMPs $\textit{in situ}$, which tunes emergency myelopoiesis and is hijacked in leukaemia.
dc.description.sponsorshipThis work was supported by NIH K01DK098315 award to E.M.P.; a Bloodwise and CRUK program grants and Wellcome Trust funding to the Cambridge Stem Cell Institute to B.G.; and NIH R01HL092471, R01HL111266 and P30DK063720 grants, Rita Allen Scholar Award and Leukemia Lymphoma Society Scholar Award to E.P.
dc.languageengen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.titleMyeloid progenitor cluster formation drives emergency and leukaemic myelopoiesisen
dc.typeArticle
prism.endingPage58
prism.issueIdentifier7648en
prism.publicationDate2017en
prism.publicationNameNatureen
prism.startingPage53
prism.volume544en
dc.identifier.doi10.17863/CAM.9326
dcterms.dateAccepted2017-02-07en
rioxxterms.versionofrecord10.1038/nature21693en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-04-06en
dc.contributor.orcidGottgens, Berthold [0000-0001-6302-5705]
dc.identifier.eissn1476-4687
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (21762)
pubs.funder-project-idLeukaemia & Lymphoma Research (12029)
pubs.funder-project-idMRC (MC_PC_12009)
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (MR/M008975/1)
cam.issuedOnline2017-03-29en
rioxxterms.freetoread.startdate2017-09-29


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