Cardiac reprogramming and miRNA

2017 Fiscal Year Final Research Report

• Project/Area Number: 26293193
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Keio University
• Principal Investigator: Ieda Masaki 慶應義塾大学, 医学部(信濃町), 講師 (70296557)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 再生

Outline of Final Research Achievements

Here we found that addition of miR-133a (miR-133) to Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Mesp1 and Myocd improved cardiac reprogramming from mouse or human fibroblasts by directly repressing Snai1, a master regulator of epithelial-to-mesenchymal transition. MiR-133 overexpression with GMT generated 7-fold more beating iCMs from mouse embryonic fibroblasts, and shortened the duration to induce beating cells from 30 to 10 days, compared to GMT alone. Snai1 knockdown suppressed fibroblast genes, upregulated cardiac gene expression, and induced more contracting iCMs with GMT transduction, recapitulating the effects of miR-133 overexpression. In contrast, overexpression of Snai1 in GMT/miR-133-transduced cells maintained fibroblast signatures and inhibited generation of beating iCMs. MiR-133-mediated Snai1 repression was also critical for cardiac reprogramming in adult mouse and human cardiac fibroblasts.

Free Research Field

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