FZD4 Marks Lateral Plate Mesoderm and Signals with NORRIN to Increase Cardiomyocyte Induction from Pluripotent Stem Cell-Derived Cardiac Progenitors
| Autor: | Johannes A. Hewel, Hongbo Guo, Peter W. Zandstra, Steven Kattman, Gordon Keller, Andrew Emili, Ting Yin, Alec D. Witty, Charles Yoon, Hannah Song, Nicole Dubois, Damaris Bausch-Fluck, Andreas P. Frei, Bernd Wollscheid |
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| Rok vydání: | 2018 |
| Předmět: |
Pluripotent Stem Cells
0301 basic medicine Receptor Platelet-Derived Growth Factor alpha FZD4 cardiac development cardiac progenitor cells regenerative medicine Nerve Tissue Proteins cardiomyocytes Biology Norrin Biochemistry Regenerative medicine Article Mesoderm Transcriptome Mice 03 medical and health sciences 0302 clinical medicine cell surface capture Frizzled 4 Cell surface capture Mass spectrometry Microarray Cardiac progenitor cells Cardiomyocytes Cardiac development Genetics Animals Humans Myocytes Cardiac Eye Proteins Induced pluripotent stem cell lcsh:QH301-705.5 Wnt Signaling Pathway mass spectrometry lcsh:R5-920 Myocardium Lateral plate mesoderm Wnt signaling pathway Cell Biology Antigens Differentiation Vascular Endothelial Growth Factor Receptor-2 Frizzled Receptors Cell biology 030104 developmental biology lcsh:Biology (General) Proteome Stem cell lcsh:Medicine (General) microarray 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Stem Cell Reports, 10 (1) Stem Cell Reports Stem Cell Reports, Vol 10, Iss 1, Pp 87-100 (2018) |
| ISSN: | 2213-6711 |
| DOI: | 10.1016/j.stemcr.2017.11.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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