Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors

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 si...

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Bibliographic Details
Published in:Cell stem cell Vol. 18; no. 3; p. 354
Main Authors: Lalit, Pratik A, Salick, Max R, Nelson, Daryl O, Squirrell, Jayne M, Shafer, Christina M, Patel, Neel G, Saeed, Imaan, Schmuck, Eric G, Markandeya, Yogananda S, Wong, Rachel, Lea, Martin R, Eliceiri, Kevin W, Hacker, Timothy A, Crone, Wendy C, Kyba, Michael, Garry, Daniel J, Stewart, Ron, Thomson, James A, Downs, Karen M, Lyons, Gary E, Kamp, Timothy J
Format: Journal Article
Language:English
Published: United States 03.03.2016
Subjects:
Animals
Cell Proliferation
Cell Survival
Cellular Reprogramming
Cellular Reprogramming Techniques - methods
Fibroblasts - cytology
Fibroblasts - metabolism
Mice
Mice, Transgenic
Myoblasts, Cardiac - cytology
Myoblasts, Cardiac - metabolism
Transcription Factors - biosynthesis
Transcription Factors - genetics
ISSN:1875-9777, 1875-9777
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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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ISSN:1875-9777
1875-9777
DOI:10.1016/j.stem.2015.12.001