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Calcineurin A gamma and NFATc3/SRPX2 axis contribute to human embryonic stem cell differentiation

Hao Chen1, Yanwu Zeng2, Min Shao1

  • 1CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, CAS Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Journal of Cellular Physiology
|January 4, 2021
PubMed

Insights

Calcineurin-NFAT signaling, specifically calcineurin A gamma and the NFATc3/SRPX2 axis, regulates human embryonic stem cell (hESC) fate. This pathway controls key markers for cell lineage and epithelial-mesenchymal transition (EMT).

Area of Science:

  • Stem cell biology
  • Molecular signaling pathways
  • Developmental biology

Background:

  • Understanding human embryonic stem cell (hESC) regulation is crucial for regenerative medicine.
  • Calcineurin-NFAT signaling is implicated in various biological processes but its role in hESC fate is undefined.

Purpose of the Study:

  • To investigate the role of calcineurin-NFAT signaling in human embryonic stem cell (hESC) fate determination.
  • To identify specific molecular players within this pathway that influence lineage commitment and epithelial-mesenchymal transition (EMT).

Main Methods:

  • Gene knockdown of calcineurin A gamma (PPP3CC) and NFATc3 in hESCs.
  • Analysis of lineage and EMT marker expression during self-renewal and differentiation.
  • Investigating protein-protein interactions (NFATc3 with c-JUN) and downstream target gene regulation (SRPX2).
  • Functional studies involving SRPX2 knockdown and co-overexpression of NFATc3/c-JUN.

Main Results:

  • Calcineurin A gamma and NFATc3 regulate expression of lineage and EMT markers in hESCs.
  • NFATc3 interacts with c-JUN, controlling the expression of SRPX2, a secreted glycoprotein.
  • SRPX2 and uPAR are involved in regulating lineage and EMT markers.
  • SRPX2 knockdown reduced marker upregulation induced by NFATc3/c-JUN co-overexpression.

Conclusions:

  • The calcineurin A gamma and NFATc3/SRPX2 axis is a novel regulator of hESC fate.
  • This pathway influences hESC differentiation by modulating lineage and EMT marker expression.
  • Findings provide new insights into the molecular mechanisms governing stem cell pluripotency and differentiation.
Keywords:
NFATc3SRPX2calcineurin A gammahESC differentiationuPAR

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