Combined transcriptomic and phosphoproteomic analysis of BMP4 signaling in human embryonic stem cells



Papadopoulos, Angelos, Chalmantzi, Varvara, Mikhaylichenko, Olga, Hyvonen, Marko, Stellas, Dimitris, Kanhere, Aditi, Heath, John, Cunningham, Debbie L, Fotsis, Theodore and Murphy, Carol
(2021) Combined transcriptomic and phosphoproteomic analysis of BMP4 signaling in human embryonic stem cells. STEM CELL RESEARCH, 50. 102133-.

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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 ActivinA 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.

Item Type: Article
Uncontrolled Keywords: Human embryonic stem cells, Activin A, BMP4, Transcriptomics, Phosphoproteomics
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 08 Jul 2021 09:15
Last Modified: 18 Jan 2023 21:36
DOI: 10.1016/j.scr.2020.102133
Open Access URL: https://doi.org/10.1016/j.scr.2020.102133
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3129269