Human embryonic stem cells (hESCs) are an invaluable tool in the fields of embryology and regenerative medicine. Activin A and BMP4 are well-characterised growth factors implicated in pluripotency and differentiation. In the current study, hESCs are cultured in a modified version of mTeSR1, where low concentrations of Activin A substitute for TGFβ. This culture system is further used to investigate the changes induced by BMP4 on hESCs by employing a combination of transcriptomic and phosphoproteomic approaches. Results indicate that in a pluripotent state, hESCs maintain WNT signaling under negative regulation by expressing pathway inhibitors. Initial stages of differentiation are characterized by upregulation of WNT pathway ligands, TGFβ pathway inhibitors which have been shown in Xenopus to expand the BMP signaling range essential for embryonic patterning, and mesendodermal transcripts. Moreover, BMP4 enhances the phosphorylation of proteins associated with migration and transcriptional regulation. Results further indicate the vital regulatory role of Activin A and BMP4 in crucial fate decisions in hESCs.

人类胚胎干细胞（hESCs）是胚胎学和再生医学领域的宝贵工具。激活素A和BMP4是特征丰富的生长因子，与多能性和分化有关。在当前的研究中，在改良的mTeSR1版本中培养了hESC，其中低浓度的激活素A替代了TGFβ。通过结合转录组学和磷酸化蛋白质组学方法，该培养系统进一步用于研究BMP4在hESC上诱导的变化。结果表明，在多能状态下，hESC通过表达途径抑制剂在负调控下维持WNT信号传导。分化的初始阶段以非洲爪蟾中显示的WNT途径配体，TGFβ途径抑制剂的上调为特征扩展了BMP信号传导范围，这对于胚胎模式和中胚层转录本至关重要。此外，BMP4增强了与迁移和转录调控相关的蛋白质的磷酸化。结果进一步表明，激活素A和BMP4在hESC的关键命运决定中起着至关重要的调节作用。