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dc.contributor.authorDalby, Amandaen
dc.contributor.authorBallester-Beltrán, Joseen
dc.contributor.authorLincetto, Chiaraen
dc.contributor.authorMueller, Annetten
dc.contributor.authorFoad, Nicolaen
dc.contributor.authorEvans, Amandaen
dc.contributor.authorBaye, Jamesen
dc.contributor.authorTurro Bassols, Ernesten
dc.contributor.authorMoreau, Thomasen
dc.contributor.authorTijssen, Marloes Ren
dc.contributor.authorGhevaert, Cedricen
dc.date.accessioned2018-12-22T00:30:20Z
dc.date.available2018-12-22T00:30:20Z
dc.date.issued2018-12en
dc.identifier.issn2213-6711
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287363
dc.description.abstractThe production of blood cells and their precursors from human pluripotent stem cells (hPSCs) in vitro has the potential to make a significant impact upon healthcare provision. In this manuscript we demonstrate that the forward programming of hPSCs through overexpression of GATA1, FLI1 and TAL1 leads to the production of a population of progenitors that can differentiate into megakaryocyte or erythroblasts. Using “rainbow” lentiviral vectors to quantify individual transgene expression in single cells, we demonstrate that cell fate decision towards an erythroblast or megakaryocyte is dictated by the level of FLI1 expression and independent of culture conditions. Early FLI1 expression is critical to confer proliferative potential to programmed cells whilst its subsequent silencing or maintenance dictates an erythroid or megakaryocytic fate, respectively. These committed progenitors subsequently expand and mature into megakaryocytes or erythroblasts in response to thrombopoietin or erythropoietin. Our results reveal molecular mechanisms underlying hPSC forward programming and novel opportunities for application to transfusion medicine
dc.description.sponsorshipWe acknowledge funding from the BHF Cambridge Centre of Excellence (RE/13/6/30180), the Wellcome Trust (Novosang consortium) and the NHS Blood and Transplant Service
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherElsevier
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectMegakaryocytesen
dc.subjectCells, Cultureden
dc.subjectErythroid Cellsen
dc.subjectPluripotent Stem Cellsen
dc.subjectHumansen
dc.subjectErythropoietinen
dc.subjectThrombopoietinen
dc.subjectCytokinesen
dc.subjectCell Differentiationen
dc.subjectGene Silencingen
dc.subjectCell Lineageen
dc.subjectTransgenesen
dc.subjectGATA1 Transcription Factoren
dc.subjectProto-Oncogene Protein c-fli-1en
dc.subjectT-Cell Acute Lymphocytic Leukemia Protein 1en
dc.titleTranscription Factor Levels after Forward Programming of Human Pluripotent Stem Cells with GATA1, FLI1, and TAL1 Determine Megakaryocyte versus Erythroid Cell Fate Decision.en
dc.typeArticle
prism.endingPage1478
prism.issueIdentifier6en
prism.publicationDate2018en
prism.publicationNameStem cell reportsen
prism.startingPage1462
prism.volume11en
dc.identifier.doi10.17863/CAM.34667
dcterms.dateAccepted2018-11-01en
rioxxterms.versionofrecord10.1016/j.stemcr.2018.11.001en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-12en
dc.contributor.orcidDalby, Amanda [0000-0002-2831-6117]
dc.contributor.orcidBaye, James [0000-0002-0078-3688]
dc.contributor.orcidTurro, Ernest [0000-0002-1820-6563]
dc.contributor.orcidMoreau, Thomas [0000-0003-1090-6685]
dc.contributor.orcidGhevaert, Cedric [0000-0002-9251-0934]
dc.identifier.eissn2213-6711
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (via Scottish National Blood Transfusion Service (SNTBS)) (XXL9126634)
pubs.funder-project-idMRC (MC_PC_12009)
pubs.funder-project-idBritish Heart Foundation (RE/13/6/30180)
pubs.funder-project-idMRC (MC_PC_14116 v2)


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