Journal
CELL STEM CELL
Volume 8, Issue 2, Pages 228-240Publisher
CELL PRESS
DOI: 10.1016/j.stem.2010.12.008
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Funding
- National Institutes of Health [R01 HL080627, CIHR 84524, F32 HL078112]
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Efficient 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-alpha segregates mouse ESC-derived Flk-1 mesoderm into Flk-1(+)PdgfR-alpha(+) cardiac and Flk-1(+)PdgfR-alpha(-) hematopoietic subpopulations. By monitoring Flk-1 and PdgfR-alpha 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-alpha 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.
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