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mTORC2介导的细胞相互作用促进BMP4诱导的WNT激活和中皮分化

Li Tong¹, Faiza Batool¹, Yueh-Ho Chiu¹

¹Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W12 0NN, UK.

Stem cell reports

|October 17, 2025

概括

人类胚胎干细胞中拉巴胺素复合体2 (mTORC2) 破坏的机械标通过影响细胞粘附和WNT激活,损害了分化. 恢复WNT信号传递挽救了间膜体的分化,揭示了mTORC2 .

科学领域:

干细胞生物学干细胞生物学
发展的分子机制的发展.
细胞信号通路是细胞信号通路.

背景情况:

拉巴胺素复合体2 (mTORC2) 的机械性标对胚胎发育至关重要.
控制mTORC2在早期发育中的作用的精确分子机制尚未完全理解.
了解mTORC2的功能是解读发育过程和潜在治疗点的关键.

研究的目的:

研究mTORC2在人类胚胎干细胞 (hESC) 自更新和分化中的作用.
阐明在hESCs中受mTORC2影响的分子通路.
为了确定mTORC2如何影响细胞粘附和发育信号.

主要方法:

在hESC中破坏mTORC2信号传输.
对Rho/Rac信号传输动态的分析.
对E-cadherin表达和细胞粘附的评估.
评估多能标记物的表达和自我更新能力.
使用BMP4和Activin进行中皮和内皮分化试验.
使用GSK3抑制剂进行WNT通路激活分析和救援实验.

主要成果:

mTORC2的干扰会改变Rho/Rac信号,减少E-cadherin,并损害hESC中的细胞粘附.
尽管有粘附缺陷,但mTORC2缺乏的hESC在bFGF的MEF-CM中保持了自我更新和多能性标记.
在mTORC2缺乏的hESC中,分化为中皮和内皮显著受损.
差异化受损与WNT激活的减少有关,可能由细胞-细胞相互作用介导.
通过GSK3抑制直接激活WNT通路,恢复了介质皮的分化.

结论:

mTORC2在调节hESC细胞命运决定方面发挥着至关重要的作用.
由mTORC2调节的细胞间粘附,对于激活正规WNT基因至关重要.
这项研究揭示了mTORC2,细胞粘附和胚胎发育中的WNT信号之间的新联系.

关键词:

在 BMP4 中,您可以使用 BMP4.在WNT中使用WNT.细胞粘附细胞粘附细胞与细胞的相互作用.消化消化消化消化人类胚胎干细胞在 mTORC2 中,mTORC2 是指mTORC2.中皮/内皮分化的差异化.

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