Stem Cells, an international journal in the field of stem cells, recently published the latest research results of Wang Gang's research group at the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, "Stimulation of somatic cell reprogramming by ERas-Akt-FoxO1 signaling axis ". This work found that the Eras-Akt signal transduction pathway associated with cancer can produce induced pluripotent stem cells by overcoming the blocking effect of the tumor suppressor gene FoxO1 and promoting the "reprogramming" of somatic cells. Provides a new perspective. Pluripotent Stem Cells have the characteristics of self-renewal, rapid proliferation, and pluripotency to differentiate into three germ layer cells. Theoretically, they can provide an unlimited source of cells for cell therapy, which is a vitally important field of regenerative medicine research research direction. In recent years, an extremely prominent reprogramming technique is to reverse the differentiated somatic cells to induced pluripotent stem cells by exogenous overexpression of pluripotent transcription factors (Oct4, Sox2, Klf4 and c-Myc). , IPSCs). The emergence of iPSC technology has brought new hope to the research of cell therapy and many genetic diseases, but the current iPS technology still faces problems such as low induction efficiency and unclear molecular mechanism.
Under the guidance of researcher Wang Gang, doctoral student Yu Yong and others discovered through a series of molecular and cell biology methods that a gene ERas highly expressed in stem cells and certain cancer cells can accelerate the iPSC induction process and increase its production efficiency. During reprogramming, Eras is tightly coupled with Akt signal to participate in the promotion of iPSC induction, and Eras activation of Akt signal only occurs during a specific period of time during somatic cell reprogramming. Further research found that the tumor suppressor gene FoxO1 is an obstacle in the process of somatic cell reprogramming, and the promotion of iPSC by Eras-Akt signaling works by overcoming the hindrance of FoxO1. Pluripotent stem cells and cancer cells have many similarities in cell biological characteristics, such as rapid proliferation, division without differentiation, etc. Akt phosphorylation is closely related to the activation of adult stem cells and cancer stem cells. For example, phosphorylated Akt can be used as a molecular marker to distinguish between resting and activated epidermal stem cells; studies have inferred that cancer stem cells may originate in certain tissues. Normal adult stem or progenitor cells, but not normally activated Akt signal can also be used to mark the initiation of cancer cells. This study found that the change in cell fate during reprogramming may be accompanied by activation and decline of Akt signaling. As an important pathway in cancer biology, the Eras-Akt-FoxO1 signal transduction pathway also plays an active role in the process of somatic cell reprogramming. This discovery provides a new understanding of the mechanism of iPSC formation, and proposes in vivo The occurrence of cancer is most likely caused by a "reprogramming" event of cells in the body.
This research work was greatly supported by Professor Cheng Linzhao of Johns Hopkins University, Professor Gao Ping of University of Science and Technology of China, and Researchers Li Jinsong and Hu Ping of Institute of Biochemistry and Cells, and obtained the Chinese Academy of Sciences, Ministry of Science and Technology and National Natural Science Foundation Funding.
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