Reichman, David E and Park, Laura and Man, Limor and Redmond, David and Chao, Kenny and Harvey, Richard P and Taketo, Makoto M and Rosenwaks, Zev and James, Daylon (2018) Wnt inhibition promotes vascular specification of embryonic cardiac progenitors. Development, 145 (1). pp. dev159905. ISSN 0950-1991 (OA)
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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.
| Item Type: | Article |
|---|---|
| Additional Information: | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 09 Feb 2018 09:25 |
| Last Modified: | 03 Apr 2018 00:01 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/693 |
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