Wnt inhibition promotes vascular specification of embryonic cardiac progenitors.

TitleWnt inhibition promotes vascular specification of embryonic cardiac progenitors.
Publication TypeJournal Article
Year of Publication2018
AuthorsReichman DE, Park L, Man L, Redmond D, Chao K, Harvey RP, Taketo MM, Rosenwaks Z, James D
JournalDevelopment
Volume145
Issue1
Date Published2018 01 08
ISSN1477-9129
KeywordsAnimals, Embryo, Mammalian, Endothelial Cells, Heart, Humans, Mice, Mice, Transgenic, Pluripotent Stem Cells, Wnt Signaling Pathway, Wnt-5a Protein
Abstract

Several studies have demonstrated a multiphasic role for Wnt signaling during embryonic cardiogenesis and developed protocols that enrich for cardiac derivatives during 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.

DOI10.1242/dev.159905
Alternate JournalDevelopment
PubMed ID29217753
PubMed Central IDPMC5825863