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Defining the Regional and Lineage Contribution of Early Mesp1 Cardiovascular Progenitors During Mammalian Heart Development

par Chabab, Samira
Président du jury Toungouz Nevessignsky, Michel
Promoteur Blanpain, Cédric
Co-Promoteur Bondue, Antoine
Publication Non publié, 2016-05-17

Thèse de doctorat

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Résumé :

The heart arises from two sources of mesoderm progenitors, the first (FHF) and the second heart field (SHF) progenitors. Mesp1 has been proposed to mark the most primitive multipotent cardiac progenitors (MCPs) common for both heart fields. However, it remains unclear whether at the single cell level, Mesp1 progenitors represent a common progenitor for the FHF and SHF. Using mosaic tracing and inducible clonal analysis with a multicolor reporter strategy, we investigated the contribution of Mesp1 cardiovascular progenitors in a temporally controlled manner during the early gastrulation. Our data indicated that the myocardium derives from ~250 Mesp1 expressing cardiac progenitors born during gastrulation. Temporal analysis of clonally labeled Mesp1 cells revealed the existence of temporally distinct populations of Mesp1 progenitors that are restricted to either the FHF or the SHF. FHF progenitors were unipotent, while SHF progenitors, were either uni- or bipotent. Microarray and single cell RT-PCR analysis of Mesp1 progenitors revealed the existence of molecularly distinct populations of Mesp1 progenitors, consistent with their lineage and regional contribution. Moreover biophysical analysis of clonal data revealed that, despite arising at different time points and contributing to different heart regions, the temporally distinct cardiac progenitors present very similar clonal dynamics. Altogether, these results provide insights into the number of cardiac progenitors and their mode of growth. Moreover they provide evidence that heart development arises from distinct populations of unipotent and bipotent cardiac progenitors expressing Mesp1 independently at different time points during gastrulation. Our data reveal that the regional segregation and lineage restriction of cardiac progenitors occurs very early during embryonic development.