BMP4 preserves the developmental potential of mESCs through Ube2s- and Chmp4b-mediated chromosomal stability safeguarding.
BMP4 preserves the developmental potential of mESCs through Ube2s- and Chmp4b-mediated chromosomal stability safeguarding.
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BMP4 通过 Ube2s 和 Chmp4b 介导的染色体稳定性保护来保留 mESC 的发育潜力。
DOI：
10.1007/s13238-021-00896-x
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发表时间：
2022-08
期刊：
影响因子：
21.1
通讯作者：
Chen, Jiayu
中科院分区：
文献类型：
--
作者：
Wang, Mingzhu;Zhao, Kun;Liu, Meng;Wang, Mengting;Qiao, Zhibin;Yi, Shanru;Jiang, Yonghua;Kou, Xiaochen;Zhao, Yanhong;Yin, Jiqing;Li, Tianming;Wang, Hong;Jiang, Cizhong;Gao, Shaorong;Chen, Jiayu
化学成分确定的培养基被广泛用于培养小鼠胚胎干细胞（mESC），其中N2 B27作为血清的替代物起作用，并且GSK 3 β和MEK抑制剂（2 i）有助于促进基态多能性。然而，最近的研究表明，MEKi可能会导致不可逆的缺陷，损害mESCs的发育潜力。在这里，我们证明了在化学定义的条件下骨形态发生蛋白（BMP）信号的缺陷是多能性受损的主要原因之一。从机制上讲，BMP 4激活BMP信号通路可以通过调节下游靶点Ube 2s和Chmp 4 b来保护mESCs的染色体完整性和增殖能力。更重要的是，BMP 4促进了独特的体内发育潜力和长期的多能性保存。此外，BMP 4驱动的多能性改善优于减弱MEK抑制的多能性改善。综上所述，我们的研究表明适当激活BMP信号对于调节功能性多能性是必不可少的，并揭示了BMP 4应该应用于无血清培养系统。 在线版本包含补充材料，可通过10.1007/s13238-021-00896-x获取。
Chemically defined medium is widely used for culturing mouse embryonic stem cells (mESCs), in which N2B27 works as a substitution for serum, and GSK3β and MEK inhibitors (2i) help to promote ground-state pluripotency. However, recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs. Here, we demonstrated the deficient bone morphogenetic protein (BMP) signal in the chemically defined condition is one of the main causes for the impaired pluripotency. Mechanistically, activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream targets Ube2s and Chmp4b. More importantly, BMP4 promotes a distinct in vivo developmental potential and a long-term pluripotency preservation. Besides, the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression. Taken together, our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system. The online version contains supplementary material available at 10.1007/s13238-021-00896-x.
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