抑制转化生长因子β（TGF-β）信号传导可在重编程过程中替代Oct4蛋白并维持多能性。
Inhibition of transforming growth factor β (TGF-β) signaling can substitute for Oct4 protein in reprogramming and maintain pluripotency.
作者信息
Tan Fangzhi, Qian Cheng, Tang Ke, Abd-Allah Saber Mohamed, Jing Naihe
机构信息
From the State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
the Institute of Life Science, Nanchang University, Nanchang, Jiangxi 330031, China, and.
出版信息
J Biol Chem. 2015 Feb 13;290(7):4500-11. doi: 10.1074/jbc.M114.609016. Epub 2014 Dec 29.
Abstract
Mouse pluripotent stem cells (PSCs), such as ES cells and induced PSCs (iPSCs), are an excellent system to investigate the molecular and cellular mechanisms involved in early embryonic development. The signaling pathways orchestrated by leukemia inhibitor factor/STAT3, Wnt/β-catenin, and FGF/MEK/ERK play key roles in the generation of pluripotency. However, the function of TGF-β signaling in this process remains elusive. Here we show that inhibiting TGF-β signaling with its inhibitor SB431542 can substitute for Oct4 during reprogramming. Moreover, inhibiting TGF-β signaling can sustain the pluripotency of iPSCs and ES cells through modulating FGF/MEK/ERK signaling. Therefore, this study reveals a novel function of TGF-β signaling inhibition in the generation and maintenance of PSCs.
摘要
小鼠多能干细胞（PSCs），如胚胎干细胞（ES细胞）和诱导多能干细胞（iPSCs），是研究早期胚胎发育所涉及的分子和细胞机制的优良体系。由白血病抑制因子/信号转导和转录激活因子3（STAT3）、Wnt/β-连环蛋白以及成纤维细胞生长因子（FGF）/丝裂原活化蛋白激酶/细胞外信号调节激酶（MEK/ERK）精心编排的信号通路在多能性的产生中起关键作用。然而，转化生长因子-β（TGF-β）信号在此过程中的功能仍不清楚。在此我们表明，用其抑制剂SB431542抑制TGF-β信号在重编程过程中可以替代八聚体结合转录因子4（Oct4）。此外，抑制TGF-β信号可以通过调节FGF/MEK/ERK信号来维持iPSCs和ES细胞的多能性。因此，本研究揭示了抑制TGF-β信号在PSCs的产生和维持中的新功能。
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