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pubmed-article:21295278pubmed:abstractTextEfficient differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to a variety of lineages requires step-wise approaches replicating the key commitment stages found during embryonic development. Here we show that expression of PdgfR-? segregates mouse ESC-derived Flk-1 mesoderm into Flk-1(+)PdgfR-?(+) cardiac and Flk-1(+)PdgfR-?(-) hematopoietic subpopulations. By monitoring Flk-1 and PdgfR-? expression, we found that specification of cardiac mesoderm and cardiomyocytes is determined by remarkably small changes in levels of Activin/Nodal and BMP signaling. Translation to human ESCs and iPSCs revealed that the emergence of cardiac mesoderm could also be monitored by coexpression of KDR and PDGFR-? and that this process was similarly dependent on optimal levels of Activin/Nodal and BMP signaling. Importantly, we found that individual mouse and human pluripotent stem cell lines require optimization of these signaling pathways for efficient cardiac differentiation, illustrating a principle that may well apply in other contexts.lld:pubmed
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pubmed-article:21295278pubmed:authorpubmed-author:WittyAlec DADlld:pubmed
pubmed-article:21295278pubmed:copyrightInfoCopyright © 2011 Elsevier Inc. All rights reserved.lld:pubmed
pubmed-article:21295278pubmed:issnTypeElectroniclld:pubmed
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pubmed-article:21295278pubmed:volume8lld:pubmed
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pubmed-article:21295278pubmed:articleTitleStage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines.lld:pubmed
pubmed-article:21295278pubmed:affiliationMcEwen Center for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada.lld:pubmed
pubmed-article:21295278pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:21295278pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
pubmed-article:21295278pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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