Cell Stem Cell
Volume 18, Issue 3, 3 March 2016, Pages 354-367
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Article
Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors

https://doi.org/10.1016/j.stem.2015.12.001Get rights and content
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Highlights

  • Cardiac factors reprogram fibroblasts into induced cardiac progenitors cells (iCPCs)

  • Wnt and JAK/STAT signaling enables robust expansion of iCPCs

  • iCPCs differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells

  • Injected iCPCs generate myocardium in the embryonic and adult post-MI mouse heart

Summary

Several studies have reported reprogramming of fibroblasts into induced cardiomyocytes; however, reprogramming into proliferative induced cardiac progenitor cells (iCPCs) remains to be accomplished. Here we report that a combination of 11 or 5 cardiac factors along with canonical Wnt and JAK/STAT signaling reprogrammed adult mouse cardiac, lung, and tail tip fibroblasts into iCPCs. The iCPCs were cardiac mesoderm-restricted progenitors that could be expanded extensively while maintaining multipotency to differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells in vitro. Moreover, iCPCs injected into the cardiac crescent of mouse embryos differentiated into cardiomyocytes. iCPCs transplanted into the post-myocardial infarction mouse heart improved survival and differentiated into cardiomyocytes, smooth muscle cells, and endothelial cells. Lineage reprogramming of adult somatic cells into iCPCs provides a scalable cell source for drug discovery, disease modeling, and cardiac regenerative therapy.

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