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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / metabolism*
  • Eye Proteins / metabolism*
  • Frizzled Receptors / metabolism*
  • Humans
  • Mesoderm / cytology
  • Mesoderm / metabolism*
  • Mice
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism*
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Wnt Signaling Pathway

Substances

  • Antigens, Differentiation
  • Eye Proteins
  • Frizzled Receptors
  • Fzd4 protein, mouse
  • Ndph protein, mouse
  • Nerve Tissue Proteins
  • Receptor, Platelet-Derived Growth Factor alpha
  • Vascular Endothelial Growth Factor Receptor-2

Grant support