Abstract
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.
Original language | English |
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Article number | 102133 |
Journal | Stem Cell Research |
Volume | 50 |
Early online date | 18 Dec 2020 |
DOIs | |
Publication status | Published - Jan 2021 |
Bibliographical note
Funding Information: This work was supported by funding from the School of Biosciences, University of Birmingham.Keywords
- Activin A
- BMP4
- Human embryonic stem cells
- Phosphoproteomics
- Transcriptomics
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology