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Derivation of Cardiac Progenitor Cells from Embryonic Stem Cells
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Derivation of Cardiac Progenitor Cells from Embryonic Stem Cells

Published on: January 12, 2015

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Wnt inhibition promotes vascular specification of embryonic cardiac progenitors

David E Reichman1, Laura Park1, Limor Man1

  • 1Center for Reproductive Medicine, Weill Cornell Medical College, New York, NY 10065, USA.

Development (Cambridge, England)
|December 9, 2017
PubMed

Insights

Reduced Wnt signaling promotes the development of endothelial cells (ECs) from cardiac progenitor cells (CPCs). Wnt5a specifically enhances vascular specification in both human pluripotent stem cells (hPSCs) and mouse embryos.

Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Molecular Signaling

Background:

  • Wnt signaling plays a complex role in embryonic heart development.
  • Protocols exist for differentiating human pluripotent stem cells (hPSCs) into cardiac derivatives.
  • The role of Wnt signaling in cardiac progenitor cell (CPC) fate specification remains understudied.

Purpose of the Study:

  • To investigate the role of Wnt signaling in the differentiation of CPCs towards downstream fates, particularly endothelial cells (ECs).
  • To determine the impact of Wnt pathway modulation on vascular commitment during hPSC differentiation and mouse embryogenesis.

Main Methods:

  • Utilized transgenic mice and hPSCs to track CPC-derived ECs.
  • Analyzed EC-fated CPCs at various stages of hPSC differentiation.
  • Manipulated Wnt signaling activity (activation/inhibition) and Wnt5a expression.

Main Results:

  • Reduced Wnt activity was identified as a key factor in EC specification from CPCs.
  • Modulating Wnt signaling altered the degree of vascular commitment in CPCs during hPSC differentiation and mouse embryogenesis.
  • Wnt5a expression was dynamic during vascular commitment, and its ectopic expression promoted EC specification.

Conclusions:

  • Wnt signaling negatively regulates vascular commitment of CPCs.
  • Wnt5a is a critical mediator promoting vascular specification of CPCs.
  • Findings provide insights into controlling cell fate during stem cell differentiation and embryonic development.

Keywords:
Cardiac developmentCardiac differentiationCardiovascular progenitorEndothelial differentiationHuman embryonic stem cellsMouseMyocardial infarctionMyocardial scar formationNon-canonical WntWnt signalingWnt5aWound healing

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