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N-cadherin prevents the premature differentiation of anterior heart field progenitors in the pharyngeal mesodermal microenvironment

The cardiac progenitor cells (CPCs) in the anterior heart field (AHF) are located in the pharyngeal mesoderm (PM), where they expand, migrate and eventually differentiate into major cell types found in the heart, including cardiomyocytes. The mechanisms by which these progenitors are able to expand...

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Autores principales: Soh, Boon-Seng, Buac, Kristina, Xu, Huansheng, Li, Edward, Ng, Shi-Yan, Wu, Hao, Chmielowiec, Jolanta, Jiang, Xin, Bu, Lei, Li, Ronald A, Cowan, Chad, Chien, Kenneth R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260345/
https://www.ncbi.nlm.nih.gov/pubmed/25367124
http://dx.doi.org/10.1038/cr.2014.142
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author Soh, Boon-Seng
Buac, Kristina
Xu, Huansheng
Li, Edward
Ng, Shi-Yan
Wu, Hao
Chmielowiec, Jolanta
Jiang, Xin
Bu, Lei
Li, Ronald A
Cowan, Chad
Chien, Kenneth R
author_facet Soh, Boon-Seng
Buac, Kristina
Xu, Huansheng
Li, Edward
Ng, Shi-Yan
Wu, Hao
Chmielowiec, Jolanta
Jiang, Xin
Bu, Lei
Li, Ronald A
Cowan, Chad
Chien, Kenneth R
author_sort Soh, Boon-Seng
collection PubMed
description The cardiac progenitor cells (CPCs) in the anterior heart field (AHF) are located in the pharyngeal mesoderm (PM), where they expand, migrate and eventually differentiate into major cell types found in the heart, including cardiomyocytes. The mechanisms by which these progenitors are able to expand within the PM microenvironment without premature differentiation remain largely unknown. Through in silico data mining, genetic loss-of-function studies, and in vivo genetic rescue studies, we identified N-cadherin and interaction with canonical Wnt signals as a critical component of the microenvironment that facilitates the expansion of AHF-CPCs in the PM. CPCs in N-cadherin mutant embryos were observed to be less proliferative and undergo premature differentiation in the PM. Notably, the phenotype of N-cadherin deficiency could be partially rescued by activating Wnt signaling, suggesting a delicate functional interaction between the adhesion role of N-cadherin and Wnt signaling in the early PM microenvironment. This study suggests a new mechanism for the early renewal of AHF progenitors where N-cadherin provides additional adhesion for progenitor cells in the PM, thereby allowing Wnt paracrine signals to expand the cells without premature differentiation.
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spelling pubmed-42603452014-12-12 N-cadherin prevents the premature differentiation of anterior heart field progenitors in the pharyngeal mesodermal microenvironment Soh, Boon-Seng Buac, Kristina Xu, Huansheng Li, Edward Ng, Shi-Yan Wu, Hao Chmielowiec, Jolanta Jiang, Xin Bu, Lei Li, Ronald A Cowan, Chad Chien, Kenneth R Cell Res Original Article The cardiac progenitor cells (CPCs) in the anterior heart field (AHF) are located in the pharyngeal mesoderm (PM), where they expand, migrate and eventually differentiate into major cell types found in the heart, including cardiomyocytes. The mechanisms by which these progenitors are able to expand within the PM microenvironment without premature differentiation remain largely unknown. Through in silico data mining, genetic loss-of-function studies, and in vivo genetic rescue studies, we identified N-cadherin and interaction with canonical Wnt signals as a critical component of the microenvironment that facilitates the expansion of AHF-CPCs in the PM. CPCs in N-cadherin mutant embryos were observed to be less proliferative and undergo premature differentiation in the PM. Notably, the phenotype of N-cadherin deficiency could be partially rescued by activating Wnt signaling, suggesting a delicate functional interaction between the adhesion role of N-cadherin and Wnt signaling in the early PM microenvironment. This study suggests a new mechanism for the early renewal of AHF progenitors where N-cadherin provides additional adhesion for progenitor cells in the PM, thereby allowing Wnt paracrine signals to expand the cells without premature differentiation. Nature Publishing Group 2014-12 2014-11-04 /pmc/articles/PMC4260345/ /pubmed/25367124 http://dx.doi.org/10.1038/cr.2014.142 Text en Copyright © 2014 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences http://creativecommons.org/licenses/by-nc-nd/3.0 This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0
spellingShingle Original Article
Soh, Boon-Seng
Buac, Kristina
Xu, Huansheng
Li, Edward
Ng, Shi-Yan
Wu, Hao
Chmielowiec, Jolanta
Jiang, Xin
Bu, Lei
Li, Ronald A
Cowan, Chad
Chien, Kenneth R
N-cadherin prevents the premature differentiation of anterior heart field progenitors in the pharyngeal mesodermal microenvironment
title N-cadherin prevents the premature differentiation of anterior heart field progenitors in the pharyngeal mesodermal microenvironment
title_full N-cadherin prevents the premature differentiation of anterior heart field progenitors in the pharyngeal mesodermal microenvironment
title_fullStr N-cadherin prevents the premature differentiation of anterior heart field progenitors in the pharyngeal mesodermal microenvironment
title_full_unstemmed N-cadherin prevents the premature differentiation of anterior heart field progenitors in the pharyngeal mesodermal microenvironment
title_short N-cadherin prevents the premature differentiation of anterior heart field progenitors in the pharyngeal mesodermal microenvironment
title_sort n-cadherin prevents the premature differentiation of anterior heart field progenitors in the pharyngeal mesodermal microenvironment
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260345/
https://www.ncbi.nlm.nih.gov/pubmed/25367124
http://dx.doi.org/10.1038/cr.2014.142
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