Title | Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Lalit PA, Salick MR, Nelson DO, Squirrell JM, Shafer CM, Patel NG, Saeed I, Schmuck EG, Markandeya YS, Wong R, Lea MR, Eliceiri KW, Hacker TA, Crone WC, Kyba M, Garry DJ, Stewart R, Thomson JA, Downs KM, Lyons GE, Kamp TJ |
Journal | Cell Stem Cell |
Volume | 18 |
Issue | 3 |
Pagination | 354-67 |
Date Published | 2016 Mar 3 |
ISSN | 1875-9777 |
Abstract | 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. |
DOI | 10.1016/j.stem.2015.12.001 |
Alternate Journal | Cell Stem Cell |
PubMed ID | 26877223 |
PubMed Central ID | PMC4779406 |
Grant List | P51 RR000167 / RR / NCRR NIH HHS / United States R01 HL129798 / HL / NHLBI NIH HHS / United States S10 RR025644 / RR / NCRR NIH HHS / United States |