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dc.contributor.authorWilkinson, Adam Cen
dc.contributor.authorRyan, David Jen
dc.contributor.authorKucinski, Iwoen
dc.contributor.authorWang, Weien
dc.contributor.authorYang, Jianen
dc.contributor.authorNestorowa, Soniaen
dc.contributor.authorDiamanti, Evangeliaen
dc.contributor.authorTsang, Jason Cheuk-Hoen
dc.contributor.authorWang, Juexuanen
dc.contributor.authorCampos, Lia Sen
dc.contributor.authorYang, Fengtangen
dc.contributor.authorFu, Beiyuanen
dc.contributor.authorWilson, Nicolaen
dc.contributor.authorLiu, Pentaoen
dc.contributor.authorGottgens, Bertholden
dc.date.accessioned2019-07-16T23:30:55Z
dc.date.available2019-07-16T23:30:55Z
dc.date.issued2019-08en
dc.identifier.issn0301-472X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/294695
dc.description.abstractPluripotent stem cell (PSC) differentiation in vitro represents a powerful and tractable model to study mammalian development, and an unlimited source of cells for regenerative medicine. Within hematology, in vitro PSC hematopoiesis affords novel insights into blood formation and represents an exciting potential approach to generate hematopoietic and immune cell types for transplantation and transfusion. Most studies to date have focused on in vitro hematopoiesis from mouse PSCs and human PSCs. However, differences in mouse and human PSC culture protocols have complicated the translation of discoveries between these systems. We recently developed a novel chemical media formulation, Expanded Potential Stem Cell Medium (EPSCM), that maintains mouse PSCs in a unique cellular state that affords extraembryonic differentiation capacity. Herein, we demonstrate that EPSCM can be directly used to stably maintain human PSCs. We further show that human PSCs maintained in EPSCM can spontaneously form embryoid bodies and undergo in vitro hematopoiesis using a simple differentiation protocol, similar to mouse PSC differentiation. EPSCM-maintained human PSCs generated at least two hematopoietic cell populations, which displayed distinct transcriptional profiles by RNA-sequencing analysis. EPSCM also supports gene targeting using homologous recombination, affording generation of a SPI1 (PU.1) reporter PSC line to study and track in vitro hematopoiesis. EPSCM therefore provides a useful tool not only to study pluripotency but also hematopoietic cell specification and developmental-lineage commitment.
dc.description.sponsorshipWellcome Trust, Bloodwise, CRUK, MRC, National Institutes of Health
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCells, Cultureden
dc.subjectFibroblastsen
dc.subjectPluripotent Stem Cellsen
dc.subjectAnimalsen
dc.subjectHumansen
dc.subjectMiceen
dc.subjectTeratomaen
dc.subjectCulture Mediaen
dc.subjectStem Cell Transplantationen
dc.subjectCell Culture Techniquesen
dc.subjectSequence Analysis, RNAen
dc.subjectCell Cycleen
dc.subjectHematopoiesisen
dc.subjectSpecies Specificityen
dc.subjectCell Lineageen
dc.subjectGenes, Reporteren
dc.subjectEmbryoid Bodiesen
dc.subjectNeural Stem Cellsen
dc.subjectCellular Reprogramming Techniquesen
dc.subjectHuman Embryonic Stem Cellsen
dc.titleExpanded potential stem cell media as a tool to study human developmental hematopoiesis in vitro.en
dc.typeArticle
prism.endingPage12.e5
prism.publicationDate2019en
prism.publicationNameExperimental hematologyen
prism.startingPage1
prism.volume76en
dc.identifier.doi10.17863/CAM.41800
dcterms.dateAccepted2019-07-11en
rioxxterms.versionofrecord10.1016/j.exphem.2019.07.003en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-08en
dc.contributor.orcidWilkinson, Adam C [0000-0001-7406-0151]
dc.contributor.orcidKucinski, Iwo [0000-0002-9385-0359]
dc.contributor.orcidWilson, Nicola [0000-0003-0865-7333]
dc.contributor.orcidGottgens, Berthold [0000-0001-6302-5705]
dc.identifier.eissn1873-2399
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWELLCOME TRUST (105031/D/14/Z)
pubs.funder-project-idCancer Research UK (21762)
pubs.funder-project-idNational Institutes of Health (NIH) (via Pennsylvania State University) (R24DK106766)
pubs.funder-project-idWellcome Trust (206328/Z/17/Z)
pubs.funder-project-idMRC (1509287)
pubs.funder-project-idWellcome Trust (203151/Z/16/Z)
pubs.funder-project-idMRC (MC_PC_12009)
pubs.funder-project-idMRC (MR/S036113/1)
cam.orpheus.successThu Jan 30 10:41:56 GMT 2020 - Embargo updated*
rioxxterms.freetoread.startdate2020-08-31


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