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

Summary 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.
Highlights • Identified and characterized FZD4 as a new marker for lateral plate mesoderm • FZD4, in conjunction with FLK1 and PDGFRA, increases cardiomyocyte enrichment • FZD4 is expressed in the human system and shows enrichment in cardiomyocytes • NORRIN addition shows increase in cardiomyocyte output from FZD4 progenitor cells
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.