Hox-dependent coordination of mouse cardiac progenitor cell patterning and differentiation
- Aix Marseille University, France
- University of Chicago, United States
- Aix-Marseille Université, France
- CNRS-AMU, France
- Technische Universität Dresden, Germany
Abstract
Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterior and posterior SHF sub-populations at genome-wide levels and demonstrate that Hoxb1 negatively regulates differentiation in the posterior SHF. Spatial mis-expression of Hoxb1 in the anterior SHF results in hypoplastic right ventricle. Activation of Hoxb1 in embryonic stem cells arrests cardiac differentiation, whereas Hoxb1-deficient mouse embryos display premature cardiac differentiation. Moreover, ectopic differentiation in the posterior SHF of embryos lacking both Hoxb1 and its paralog Hoxa1 results in atrioventricular septal defects. Our results show that Hoxb1 plays a key role in patterning cardiac progenitor cells that contribute to both cardiac poles and provide new insights into the pathogenesis of CHD.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2 and 3.
Article and author information
Author details
Fabienne Lescroart
Magali Théveniau-Ruissy
Funding
Agence Nationale de la Recherche (ANR-13-BSV2-0003)
- Michel Puceat
- Robert G Kelly
- Stephane Zaffran
Agence Nationale de la Recherche (ANR-18-CE13-0011)
- Robert G Kelly
- Stephane Zaffran
Fondation Lefoulon Delalande
- Sonia Stefanovic
- Fabienne Lescroart
Association Française contre les Myopathies (MNH-Decrypt)
- Stephane Zaffran
Fondation pour la Recherche Médicale
- Brigitte Laforest
Fondation pour la Recherche Médicale (DEQ20150331717)
- Robert G Kelly
European Commission (H2020-MSCA-IF-2014)
- Sonia Stefanovic
Fondation Leducq (Research Equipment and Technological Platform Awards)
- Michel Puceat
- Robert G Kelly
- Stephane Zaffran
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Richard P Harvey, Victor Chang Cardiac Research Institute, Australia
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal procedures were carried out under protocols approved by a national appointed ethical committee for animal experimentation (Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche; Authorization N{degree sign}32-08102012).
Version history
- Received: January 13, 2020
- Accepted: August 16, 2020
- Accepted Manuscript published: August 17, 2020 (version 1)
- Version of Record published: September 1, 2020 (version 2)
Copyright
© 2020, Stefanovic et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Hox-dependent coordination of mouse cardiac progenitor cell patterning and differentiation
eLife 9:e55124.
https://doi.org/10.7554/eLife.55124
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