期刊
STEM CELL RESEARCH
卷 50, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.scr.2020.102133
关键词
Human embryonic stem cells; Activin A; BMP4; Transcriptomics; Phosphoproteomics
资金
- School of Biosciences, University of Birmingham
This study investigates the effects of Activin A and BMP4 on human embryonic stem cells, revealing their crucial regulatory roles in determining cell fate decisions. The findings highlight the importance of WNT signaling in maintaining pluripotency and promoting differentiation in hESCs.
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 TGF beta. This culture system is further used to investigate the changes induced by BMP4 on hESCs by employing a combination of transcriptomic and phosphopmteomic 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, TGF beta 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.
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