A single cell transcriptomic and clonal analysis depicts valvulogenesis - Archive ouverte HAL Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2022

A single cell transcriptomic and clonal analysis depicts valvulogenesis

Résumé

Mitral valve prolapse is often associated with several congenital heart malformations. During development, endocardial cells of the atrioventricular canal undergo endothelial to mesenchymal transition (EndMT) to give rise to the different mitral valvular cells. However, our understanding of the identity and fate decisions of these endocardial cells during development is lacking. Here, using single-cell RNA sequencing (scRNA-seq) of genetically labeled AVC endocardial cells at E9.5 in murine heart, we uncovered and genetically characterized a restricted population of pro-EndMT cells and further distinct populations of valve progenitors that together contribute to different endothelial and interstitial valvular cells in E16.5 embryonic and P0 postnatal murine mitral valve. Moreover, by genetically labeling endocardial cells using CAG ERT2Cre+/- / Brainbow +/- mice at embryonic stage E8.5, prior to EndMT, we observed specific modes of growth of endocardial derived clones in E16.5 embryonic mitral valve. Collectively, our data reveal the identity of specified endocardial cells and the distinct types of clonal contribution of these cells to the formation of the mitral valve. They further open the path towards finding new cell targets for a therapeutic approach of congenital and acquired valve diseases.

Dates et versions

hal-03875426 , version 1 (28-11-2022)

Identifiants

Citer

Batoul Farhat, Ignacio Bordeu, Bernd Jagla, Hugo Blanc, Jean Livet, et al.. A single cell transcriptomic and clonal analysis depicts valvulogenesis. 2022. ⟨hal-03875426⟩
16 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More