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GFRA2 Identifies Cardiac Progenitors and Mediates Cardiomyocyte Differentiation in a RET-Independent Signaling Pathway

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-de...

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Autores principales: Ishida, Hidekazu, Saba, Rie, Kokkinopoulos, Ioannis, Hashimoto, Masakazu, Yamaguchi, Osamu, Nowotschin, Sonja, Shiraishi, Manabu, Ruchaya, Prashant, Miller, Duncan, Harmer, Stephen, Poliandri, Ariel, Kogaki, Shigetoyo, Sakata, Yasushi, Dunkel, Leo, Tinker, Andrew, Hadjantonakis, Anna-Katerina, Sawa, Yoshiki, Sasaki, Hiroshi, Ozono, Keiichi, Suzuki, Ken, Yashiro, Kenta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967477/
https://www.ncbi.nlm.nih.gov/pubmed/27396331
http://dx.doi.org/10.1016/j.celrep.2016.06.050
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author Ishida, Hidekazu
Saba, Rie
Kokkinopoulos, Ioannis
Hashimoto, Masakazu
Yamaguchi, Osamu
Nowotschin, Sonja
Shiraishi, Manabu
Ruchaya, Prashant
Miller, Duncan
Harmer, Stephen
Poliandri, Ariel
Kogaki, Shigetoyo
Sakata, Yasushi
Dunkel, Leo
Tinker, Andrew
Hadjantonakis, Anna-Katerina
Sawa, Yoshiki
Sasaki, Hiroshi
Ozono, Keiichi
Suzuki, Ken
Yashiro, Kenta
author_facet Ishida, Hidekazu
Saba, Rie
Kokkinopoulos, Ioannis
Hashimoto, Masakazu
Yamaguchi, Osamu
Nowotschin, Sonja
Shiraishi, Manabu
Ruchaya, Prashant
Miller, Duncan
Harmer, Stephen
Poliandri, Ariel
Kogaki, Shigetoyo
Sakata, Yasushi
Dunkel, Leo
Tinker, Andrew
Hadjantonakis, Anna-Katerina
Sawa, Yoshiki
Sasaki, Hiroshi
Ozono, Keiichi
Suzuki, Ken
Yashiro, Kenta
author_sort Ishida, Hidekazu
collection PubMed
description 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.
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spelling pubmed-49674772016-08-04 GFRA2 Identifies Cardiac Progenitors and Mediates Cardiomyocyte Differentiation in a RET-Independent Signaling Pathway Ishida, Hidekazu Saba, Rie Kokkinopoulos, Ioannis Hashimoto, Masakazu Yamaguchi, Osamu Nowotschin, Sonja Shiraishi, Manabu Ruchaya, Prashant Miller, Duncan Harmer, Stephen Poliandri, Ariel Kogaki, Shigetoyo Sakata, Yasushi Dunkel, Leo Tinker, Andrew Hadjantonakis, Anna-Katerina Sawa, Yoshiki Sasaki, Hiroshi Ozono, Keiichi Suzuki, Ken Yashiro, Kenta Cell Rep Article 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. Cell Press 2016-07-07 /pmc/articles/PMC4967477/ /pubmed/27396331 http://dx.doi.org/10.1016/j.celrep.2016.06.050 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ishida, Hidekazu
Saba, Rie
Kokkinopoulos, Ioannis
Hashimoto, Masakazu
Yamaguchi, Osamu
Nowotschin, Sonja
Shiraishi, Manabu
Ruchaya, Prashant
Miller, Duncan
Harmer, Stephen
Poliandri, Ariel
Kogaki, Shigetoyo
Sakata, Yasushi
Dunkel, Leo
Tinker, Andrew
Hadjantonakis, Anna-Katerina
Sawa, Yoshiki
Sasaki, Hiroshi
Ozono, Keiichi
Suzuki, Ken
Yashiro, Kenta
GFRA2 Identifies Cardiac Progenitors and Mediates Cardiomyocyte Differentiation in a RET-Independent Signaling Pathway
title GFRA2 Identifies Cardiac Progenitors and Mediates Cardiomyocyte Differentiation in a RET-Independent Signaling Pathway
title_full GFRA2 Identifies Cardiac Progenitors and Mediates Cardiomyocyte Differentiation in a RET-Independent Signaling Pathway
title_fullStr GFRA2 Identifies Cardiac Progenitors and Mediates Cardiomyocyte Differentiation in a RET-Independent Signaling Pathway
title_full_unstemmed GFRA2 Identifies Cardiac Progenitors and Mediates Cardiomyocyte Differentiation in a RET-Independent Signaling Pathway
title_short GFRA2 Identifies Cardiac Progenitors and Mediates Cardiomyocyte Differentiation in a RET-Independent Signaling Pathway
title_sort gfra2 identifies cardiac progenitors and mediates cardiomyocyte differentiation in a ret-independent signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967477/
https://www.ncbi.nlm.nih.gov/pubmed/27396331
http://dx.doi.org/10.1016/j.celrep.2016.06.050
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