期刊
STEM CELLS
卷 30, 期 7, 页码 1405-1413出版社
WILEY
DOI: 10.1002/stem.1121
关键词
miR-199a-3p; p53; Induced pluripotent stem cells; MicroRNAs processing; Efficiency
资金
- Chinese Academy of Sciences Grant [XDA01020104]
- National Natural Science Foundation of China [31030046, 31171316]
- Ministry of Science and Technology of China [2010CB912804, 2011CB966302, 2011CBA01103]
Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by ectopic expression of defined transcriptional factors. The efficiency of this process, however, is extremely low. Although inactivation of p53 has been recently shown to greatly enhance reprogramming efficiency, the underlying molecular mechanisms still remain largely unknown. Here, we report that miR-199a-3p is upregulated by p53 at the post-transcriptional level. Induction of miR-199a-3p significantly decreases reprogramming efficiency, whereas miR-199a-3p inhibition greatly enhances it. Mechanistically, miR-199a-3p overexpression inhibits cell proliferation by imposing G1 cell cycle arrest. Conversely, miR-199a-3p inhibition results in a pronounced increase in cell proliferation. Furthermore, the enhancement in reprogramming of p53 knockdown cells is almost completely reversed with replacement of miR-199a-3p. Also, miR-199a-3p inhibition partially rescues iPS generation impaired by p53. These findings suggest miR-199a-3p as a novel p53 target that negatively regulates somatic cell reprogramming. STEM CELLS 2012;30:1405-1413
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