Abstract:
Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells 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.
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