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

Charles Yoon, Hannah Song, Ting Yin, Damaris Bausch-Fluck, Andreas P. Frei, Steven Kattman, Nicole Dubois, Alec D. Witty, Johannes A. Hewel, Hongbo Guo, Andrew Emili, Bernd Wollscheid, Gordon Keller, Peter W. Zandstra

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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. In this article, Zandstra and colleagues have identified FZD4 as a new marker for lateral plate mesoderm. Using FZD4, they showed an increase in cardiac progenitor cell purity and a subsequent increase in cardiomyocyte induction in both the mouse and human systems. These findings demonstrate a role for FZD4 in mammalian cardiac development.

Original languageEnglish
Pages (from-to)87-100
Number of pages14
JournalStem Cell Reports
Volume10
Issue number1
DOIs
StatePublished - 2018
Externally publishedYes

Keywords

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

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