2013 Fiscal Year Final Research Report
Direct reprogramming of human fibroblasts into cardiomyocyte-like cells
| Project/Area Number |
23659426
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
IEDA Masaki 慶應義塾大学, 医学部, 特任講師 (70296557)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 心臓 / 再生 |
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| Research Abstract |
Direct reprogramming of differentiated human somatic cells into cardiac cells holds great promise for regenerative medicine. It has not been whether human fibroblasts can be directly reprogrammed into differentiated cardiomyocytes by defined factors. Here, we demonstrate that Gata4, Mef2c, and Tbx5 could also convert postnatal human cardiac fibroblasts directly into cardiomyocyte-like cells, when combined with two additional cardiac transcriptional regulators. Human induced cardiac cells expressed multiple cardiac-specific markers, changed a global gene expression profile toward a cardiomyocyte-like state, and generated spontaneous Ca transients. Importantly, a subset of induced cardiac cells matured to exhibit action potentials and contracted synchronously when co-cultured with primary murine cardiomyocytes. Thus, human fibroblasts can be converted into cardiomyocyte-like cells and these methods may facilitate future applications in regenerative purposes.
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