Highly Efficient miRNA-Mediated Reprogramming of Mouse and Human Somatic Cells to Pluripotency

Abstract

Transcription factor-based cellular reprogramming has opened the way to converting somatic cells to a pluripotent state, but has faced limitations resulting from the requirement for transcription factors and the relative inefficiency of the process. We show here that expression of the miR302/367 cluster rapidly and efficiently reprograms mouse and human somatic cells to an iPSC state without a requirement for exogenous transcription factors. This miRNA-based reprogramming approach is two orders of magnitude more efficient than standard Oct4/Sox2/Klf4/Myc-mediated methods. Mouse and human miR302/367 iPSCs display similar characteristics to Oct4/Sox2/Klf4/Myc-iPSCs, including pluripotency marker expression, teratoma formation, and, for mouse cells, chimera contribution and germline contribution. We found that miR367 expression is required for miR302/367-mediated reprogramming and activates Oct4 gene expression, and that suppression of Hdac2 is also required. Thus, our data show that miRNA and Hdac-mediated pathways can cooperate in a powerful way to reprogram somatic cells to pluripotency.PaperFlickeyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI4ZjQ2OTBmMDY1YTBjOGVlYjdkOTI0NWZlNGVkYzA5MCIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc3OTc3ODkxfQ.dbKbsGf3Tt9wpqwsR2YK4MVriDUBB0Fy9_GheRxv7pJ0rKbu39d7cVr_lHP_Wbj8xMOOs20MeWQXDfoZabA9zX7HHB88NBkCLZXICckJx43j3Wa7a78lmwk446cKLHR1otWsHddTold7WzmDh8ISMNFL7b67z3RrrrLYOnXxivRw0SBv9YtdSGEAilINYED8PU4_ycTg6Sag7Gq92rsqvXqFUWB8SWVJgRWZzbgzyQ5T5h6TT23b6XFQvLOPMNiu_NuqoFwgRwKByUHudZ6RlWYKS2u2E8p1ZHqG7S21C9jv5D3kURFecyEL12lmv4c4x6ZtLY8e8Vaccs2eQsnStg(mp4, (10.95 MB) Download video