Researchers from the Chinese Academy of Medical Sciences and Peking Union Medical College found that the pro-apoptotic protein PUMA as a target of p53 participates in inhibiting somatic cell reprogramming, and inhibiting this molecule may increase the efficiency of somatic cell reprogramming. Related research papers were published in the journal Nature Communications on July 22. Professor Tao Cheng from the Peking Union Medical College of the Chinese Academy of Medical Sciences is a specially appointed professor (Yangtze River Scholar) of the Ministry of Education. He is good at diagnosis and treatment of hematopoietic stem cells, and has made remarkable achievements in the research of stem cell biology and tumor stem cell projects. In the past 5 years, more than 20 journal articles have been published in international journals, all of which are included in SCI, and others cited 591 times. In 2006, Professor Shinya Yamanaka of Kyoto University in Japan first used retroviruses to introduce four transcription factors into fully differentiated mouse fibroblasts, reorganizing them into totipotent embryonic cells, and These rearranged cells of "rejuvenation" are named "induced pluripotent stem cells" (iPS cells). iPS cells and ES cells have similar functions and have advantages over ES cells. iPS cells can be generated by somatic cells, thus circumventing many ethical and legal obstacles that ES cell research has always faced. Yamanaka Yamanaka won the 2012 Nobel Prize in Physiology or Medicine for his achievements. Although this technology makes it possible for adult cells to "return to old age" to become stem cells, and shows a broad medical application prospect. Various iPS cell researches around the world are in full swing, but it is not easy to apply them to clinical practice. Scientists have been trapped for a long time by obstacles such as low efficiency, slow speed, and complicated composition of iPS cells. Little is known about the underlying mechanism of the somatic cell reprogramming process. Some studies in recent years have found that the p53 signaling pathway has an obstructive effect on the reprogramming of cells. Inhibiting the function of p53 will greatly increase the productivity of mouse and human pluripotent stem cells. Therefore, analyzing the regulatory mechanism of p53 cell network has become a new research direction of somatic cell reprogramming. p21Cdkn1a (p21) is a major target of p53. It has also been confirmed that p53 inhibits iPS cell production at least in part due to p21-mediated cell cycle arrest. Therefore, scientists have been working to find other targets for p53 that regulate this reprogramming process. In this paper, the researchers examined the role of p53 pro-apoptotic mediator PUMA compared to p21 in the p53 signaling pathway in somatic cell reprogramming. Using mouse strains lacking these molecules, the researchers confirmed that PUMA mediates the inhibitory effect of p53 on iPS cell production independently of p21. Compared with p21 or p53-deleted iPS cells, PUMA-deleted iPS cells have less DNA damage and chromosomal instability, thereby increasing the survival rate of the cells. These findings indicate that PUMA may be a more ideal target for inhibiting p53 signaling to induce the generation of pluripotent stem cells, which is of great significance for the development of new iPS technology and the promotion of iPS cells for clinical treatment.
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