deficiency 1-5 . So far, p21 is the only p53 target shown to contribute to p53 repression of iPSC... more deficiency 1-5 . So far, p21 is the only p53 target shown to contribute to p53 repression of iPSC (induced pluripotent stem cell) generation 1,3 , indicating that additional p53 targets may regulate this process. Here, we demonstrate that miR-34 microRNAs (miRNAs), particularly miR-34a, exhibit p53-dependent induction during reprogramming. Mir34a deficiency in mice significantly increased reprogramming efficiency and kinetics, with miR-34a and p21 cooperatively regulating somatic reprogramming downstream of p53. Unlike p53 deficiency, which enhances reprogramming at the expense of iPSC pluripotency, genetic ablation of Mir34a promoted iPSC generation without compromising self-renewal or differentiation. Suppression of reprogramming by miR-34a was due, at least in part, to repression of pluripotency genes, including Nanog, Sox2 and Mycn (also known as N-Myc ). This post-transcriptional gene repression by miR-34a also regulated iPSC differentiation kinetics. miR-34b and c similarly repressed reprogramming; and all three miR-34 miRNAs acted cooperatively in this process. Taken together, our findings identified miR-34 miRNAs as p53 targets that play an essential role in restraining somatic reprogramming. ; ref. 6). This reprogramming process is rooted in the remarkable cellular plasticity retained during differentiation. The process can be triggered by exogenous expression of a set of defined ESC-specific transcription factors, Pou5f1 (also known as Oct4), Sox2, Klf4 and c-Myc (refs 6-9), which constitute the core regulatory circuits controlling pluripotency and self-renewal. Enforced expression of these reprogramming factors
deficiency 1-5 . So far, p21 is the only p53 target shown to contribute to p53 repression of iPSC... more deficiency 1-5 . So far, p21 is the only p53 target shown to contribute to p53 repression of iPSC (induced pluripotent stem cell) generation 1,3 , indicating that additional p53 targets may regulate this process. Here, we demonstrate that miR-34 microRNAs (miRNAs), particularly miR-34a, exhibit p53-dependent induction during reprogramming. Mir34a deficiency in mice significantly increased reprogramming efficiency and kinetics, with miR-34a and p21 cooperatively regulating somatic reprogramming downstream of p53. Unlike p53 deficiency, which enhances reprogramming at the expense of iPSC pluripotency, genetic ablation of Mir34a promoted iPSC generation without compromising self-renewal or differentiation. Suppression of reprogramming by miR-34a was due, at least in part, to repression of pluripotency genes, including Nanog, Sox2 and Mycn (also known as N-Myc ). This post-transcriptional gene repression by miR-34a also regulated iPSC differentiation kinetics. miR-34b and c similarly repressed reprogramming; and all three miR-34 miRNAs acted cooperatively in this process. Taken together, our findings identified miR-34 miRNAs as p53 targets that play an essential role in restraining somatic reprogramming. ; ref. 6). This reprogramming process is rooted in the remarkable cellular plasticity retained during differentiation. The process can be triggered by exogenous expression of a set of defined ESC-specific transcription factors, Pou5f1 (also known as Oct4), Sox2, Klf4 and c-Myc (refs 6-9), which constitute the core regulatory circuits controlling pluripotency and self-renewal. Enforced expression of these reprogramming factors
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Papers by Yingchao Zhong