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Wnt inhibition promotes vascular specification of embryonic cardiac progenitors.

Authors
  • Reichman, David E1
  • Park, Laura1
  • Man, Limor1
  • Redmond, David2
  • Chao, Kenny1
  • Harvey, Richard P3, 4, 5
  • Taketo, Makoto M6
  • Rosenwaks, Zev1
  • James, Daylon7, 8
  • 1 Center for Reproductive Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
  • 2 Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10065, USA.
  • 3 Developmental and Stem Cell Biology Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia. , (Australia)
  • 4 St. Vincent's Clinical School, University of New South Wales, Kensington 2052, Australia. , (Australia)
  • 5 School of Biological and Biomolecular Sciences, University of New South Wales, Kensington 2052, Australia. , (Australia)
  • 6 Department of Pharmacology, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto 606-8501, Japan. , (Japan)
  • 7 Center for Reproductive Medicine, Weill Cornell Medical College, New York, NY 10065, USA [email protected]
  • 8 Tri-Institutional Stem Cell Derivation Laboratory, Weill Cornell Medical College, New York, NY 10065, USA.
Type
Published Article
Journal
Development
Publisher
The Company of Biologists
Publication Date
Jan 08, 2018
Volume
145
Issue
1
Identifiers
DOI: 10.1242/dev.159905
PMID: 29217753
Source
Medline
Keywords
License
Unknown

Abstract

Several studies have demonstrated a multiphasic role for Wnt signaling during embryonic cardiogenesis and developed protocols that enrich for cardiac derivatives during in vitro differentiation of human pluripotent stem cells (hPSCs). However, few studies have investigated the role of Wnt signaling in the specification of cardiac progenitor cells (CPCs) toward downstream fates. Using transgenic mice and hPSCs, we tracked endothelial cells (ECs) that originated from CPCs expressing NKX2.5. Analysis of EC-fated CPCs at discrete phenotypic milestones during hPSC differentiation identified reduced Wnt activity as a hallmark of EC specification, and the enforced activation or inhibition of Wnt reduced or increased, respectively, the degree of vascular commitment within the CPC population during both hPSC differentiation and mouse embryogenesis. Wnt5a, which has been shown to exert an inhibitory influence on Wnt signaling during cardiac development, was dynamically expressed during vascular commitment of hPSC-derived CPCs, and ectopic Wnt5a promoted vascular specification of hPSC-derived and mouse embryonic CPCs.

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