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Stem Cell Reports. 2018 Jan 9;10(1):87-100. doi: 10.1016/j.stemcr.2017.11.008. Epub 2017 Dec 14.

FZD4 Marks Lateral Plate Mesoderm and Signals with NORRIN to Increase Cardiomyocyte Induction from Pluripotent Stem Cell-Derived Cardiac Progenitors.

Author information

1
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
2
Institute of Molecular Systems Biology at the Department of Health Sciences and Technology, Zurich 8092, Switzerland.
3
McEwen Centre for Regenerative Medicine, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
4
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
5
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Centre for Commercialization of Regenerative Medicine, Toronto, ON M5G 1M1, Canada; Medicine by Design: A Canada First Research Excellence Fund Program, University of Toronto, Toronto, ON M5G 1M1, Canada. Electronic address: peter.zandstra@utoronto.ca.

Abstract

The identification of cell surface proteins on stem cells or stem cell derivatives is a key strategy for the functional characterization, isolation, and understanding of stem cell population dynamics. Here, using an integrated mass spectrometry- and microarray-based approach, we analyzed the surface proteome and transcriptome of cardiac progenitor cells (CPCs) generated from the stage-specific differentiation of mouse and human pluripotent stem cells. Through bioinformatics analysis, we have identified and characterized FZD4 as a marker for lateral plate mesoderm. Additionally, we utilized FZD4, in conjunction with FLK1 and PDGFRA, to further purify CPCs and increase cardiomyocyte (CM) enrichment in both mouse and human systems. Moreover, we have shown that NORRIN presented to FZD4 further increases CM output via proliferation through the canonical WNT pathway. Taken together, these findings demonstrate a role for FZD4 in mammalian cardiac development.

KEYWORDS:

Frizzled 4; Norrin; cardiac development; cardiac progenitor cells; cardiomyocytes; cell surface capture; mass spectrometry; microarray; regenerative medicine

PMID:
29249665
PMCID:
PMC5768897
DOI:
10.1016/j.stemcr.2017.11.008
[Indexed for MEDLINE]
Free PMC Article

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