Li Wenlin, Wei Wanguo, Ding Sheng
Department of Cell Biology, Second Military Medical University, Shanghai, 200433, China.
Stem Cell and Regenerative Medicine Center, Chinese Academy of Science, Shanghai Advanced Research Institute, Shanghai, 201210, China.
Methods Mol Biol. 2016;1344:137-45. doi: 10.1007/978-1-4939-2966-5_8.
The transforming growth factor-β (TGF-β) family of cytokines, including TGF-β, bone morphogenic proteins (BMPs), and activin/nodal, is a group of crucial morphogens in embryonic development, and plays key roles in modulating stem/progenitor cell fate. TGF-β signaling is essential in maintaining the pluripotency of human pluripotent stem cells (hPSCs), including both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), and its modulation can direct lineage-specific differentiation. Recent studies also demonstrate TGF-β signaling negatively regulates reprogramming and inhibition of TGF-β signaling can enhance reprogramming through facilitating mesenchymal-to-epithelial transition (MET). This chapter introduces methods of modulating somatic cell reprogramming to iPSCs and neural induction from hPSCs through modulating TGF-β signaling by chemical approaches.
细胞因子转化生长因子-β(TGF-β)家族,包括TGF-β、骨形态发生蛋白(BMP)和激活素/节点蛋白,是胚胎发育中一组关键的形态发生素,在调节干细胞/祖细胞命运中起关键作用。TGF-β信号传导对于维持人类多能干细胞(hPSC)的多能性至关重要,hPSC包括人类胚胎干细胞(hESC)和人类诱导多能干细胞(hiPSC),其调节可指导谱系特异性分化。最近的研究还表明,TGF-β信号传导对重编程起负调节作用,抑制TGF-β信号传导可通过促进间充质向上皮转变(MET)来增强重编程。本章介绍了通过化学方法调节TGF-β信号传导,将体细胞重编程为诱导多能干细胞以及从人类多能干细胞进行神经诱导的方法。