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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 376-388 |
| Number of pages | 13 |
| Journal | Cell Stem Cell |
| Volume | 8 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 8 2011 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Cell Biology
- Molecular Medicine
- Genetics
Cite this
Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. / Anokye-Danso, Frederick; Trivedi, Chinmay M.; Juhr, Denise; Gupta, Mudit; Cui, Zheng; Tian, Ying; Zhang, Yuzhen; Yang, Wenli; Gruber, Peter J.; Epstein, Jonathan A.; Morrisey, Edward E.
In: Cell Stem Cell, Vol. 8, No. 4, 08.04.2011, p. 376-388.Research output: Contribution to journal › Article
}
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.
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 -