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The activation of BMP and WNT signals specifies epicardial lineage from hESCs

 

The epicardium plays an important role during development process of heart and tissue regeneration after cardiac injury. Witty et al. describe a new strategy of using human pluripotent stem cells (hESCs) to generate epicardial lineage cells by activation the BMP and WNT signaling pathways in a stage-specific way. The article was published on Nature Biotechnology, recently.

 

During early stage of cardiac development, two distinct cell populations, endocardium and myocardium, arise. Soon after the two cell populations form the four-chambered heart, the third population, epicardium, starts to develop. The epicardium then undergoes a signal-induced epithelial-to-mesenchymal transition (EMT). Researchers discovered both BMP and canonical WNT signaling pathways are required in the development of pro-epicardial (P-Epi) cells from hESCs. In the present of TGFB and bFGF signals, passaged Epi cells had ability to undergo EMT. Otherwise, Epi cells synthesized retinoic acid through the upregulation of ALDH1A2.

 

In addition, their finding indicates BMP pathway is essential in both cardiomyocyte and epicardial determination. Interestingly, in the presence of WNT signaling, epicardial lineage is generated, whereas the cardiomyocyte fate is determined without WNT. Overall, the results identify BMP and WNT as critical signaling pathways in regulation of cardiomyocyte and epicardial lineages determination, from hPSC-derived mesoderm.

 

Reference:
Nat Biotechnol. 2014 Oct; 32(10): 126-35

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