TY - JOUR
T1 - Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency
AU - Anokye-Danso, Frederick
AU - Trivedi, Chinmay M.
AU - Juhr, Denise
AU - Gupta, Mudit
AU - Cui, Zheng
AU - Tian, Ying
AU - Zhang, Yuzhen
AU - Yang, Wenli
AU - Gruber, Peter J.
AU - Epstein, Jonathan A.
AU - Morrisey, Edward E.
N1 - Funding Information:
These studies were supported by funding from the NIH to E.E.M. (HL064632, HL087825, and HL100405), J.A.E. (HL071546 and HL100405), C.M.T. (HL098366), and an American Heart Association Jon Holden DeHaan Myogenesis Center Award to E.E.M. and J.A.E. The authors thank K. Zaret for the Rosa26-lacZ MEFs and gratefully acknowledge the support of the Penn Institute for Regenerative Medicine during these studies.
PY - 2011/4/8
Y1 - 2011/4/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79953881831&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953881831&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2011.03.001
DO - 10.1016/j.stem.2011.03.001
M3 - Article
C2 - 21474102
AN - SCOPUS:79953881831
VL - 8
SP - 376
EP - 388
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 4
ER -