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

Research output: Contribution to journalArticlepeer-review

Authors

  • Angelos Papadopoulos
  • Varvara Chalmantzi
  • Olga Mikhaylichenko
  • Dimitris Stellas
  • Marko Hyvonen
  • Theodore Fotsis

Colleges, School and Institutes

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.

Bibliographic note

Funding Information: This work was supported by funding from the School of Biosciences, University of Birmingham.

Details

Original languageEnglish
Article number102133
JournalStem Cell Research
Volume50
Early online date18 Dec 2020
Publication statusPublished - Jan 2021

Keywords

  • Activin A, BMP4, Human embryonic stem cells, Phosphoproteomics, Transcriptomics

ASJC Scopus subject areas

Sustainable Development Goals