GFRA2 identifies cardiac progenitors and mediates cardiomyocyte differentiation in a RET-independent signaling pathway Journal Article


Authors: Ishida, H.; Saba, R.; Kokkinopoulos, I.; Hashimoto, M.; Yamaguchi, O.; Nowotschin, S.; Shiraishi, M.; Ruchaya, P.; Miller, D.; Harmer, S.; Poliandri, A.; Kogaki, S.; Sakata, Y.; Dunkel, L.; Tinker, A.; Hadjantonakis, A. K.; Sawa, Y.; Sasaki, H.; Ozono, K.; Suzuki, K.; Yashiro, K.
Article Title: GFRA2 identifies cardiac progenitors and mediates cardiomyocyte differentiation in a RET-independent signaling pathway
Abstract: A surface marker that distinctly identifies cardiac progenitors (CPs) is essential for the robust isolation of these cells, circumventing the necessity of genetic modification. Here, we demonstrate that a Glycosylphosphatidylinositol-anchor containing neurotrophic factor receptor, Glial cell line-derived neurotrophic factor receptor alpha 2 (Gfra2), specifically marks CPs. GFRA2 expression facilitates the isolation of CPs by fluorescence activated cell sorting from differentiating mouse and human pluripotent stem cells. Gfra2 mutants reveal an important role for GFRA2 in cardiomyocyte differentiation and development both in vitro and in vivo. Mechanistically, the cardiac GFRA2 signaling pathway is distinct from the canonical pathway dependent on the RET tyrosine kinase and its established ligands. Collectively, our findings establish a platform for investigating the biology of CPs as a foundation for future development of CP transplantation for treating heart failure. © 2016 The Author(s)
Journal Title: Cell Reports
Volume: 16
Issue: 4
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2016-07-26
Start Page: 1026
End Page: 1038
Language: English
DOI: 10.1016/j.celrep.2016.06.050
PROVIDER: scopus
PMCID: PMC4967477
PUBMED: 27396331
DOI/URL:
Notes: Article -- Export Date: 6 December 2016 -- Source: Scopus
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