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© Service photographie
Vue sur les capillaires d'un séquenceur d'ADN de la Plate Forme Génomique.
Publication : Nature communications

Human pre-valvular endocardial cells derived from pluripotent stem cells recapitulate cardiac pathophysiological valvulogenesis

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature communications - 26 Apr 2019

Neri T, Hiriart E, van Vliet PP, Faure E, Norris RA, Farhat B, Jagla B, Lefrancois J, Sugi Y, Moore-Morris T, Zaffran S, Faustino RS, Zambon AC, Desvignes JP, Salgado D, Levine RA, de la Pompa JL, Terzic A, Evans SM, Markwald R, Pucéat M

Link to Pubmed [PMID] – 31028265

Nat Commun 2019 04;10(1):1929

Genetically modified mice have advanced our understanding of valve development and disease. Yet, human pathophysiological valvulogenesis remains poorly understood. Here we report that, by combining single cell sequencing and in vivo approaches, a population of human pre-valvular endocardial cells (HPVCs) can be derived from pluripotent stem cells. HPVCs express gene patterns conforming to the E9.0 mouse atrio-ventricular canal (AVC) endocardium signature. HPVCs treated with BMP2, cultured on mouse AVC cushions, or transplanted into the AVC of embryonic mouse hearts, undergo endothelial-to-mesenchymal transition and express markers of valve interstitial cells of different valvular layers, demonstrating cell specificity. Extending this model to patient-specific induced pluripotent stem cells recapitulates features of mitral valve prolapse and identified dysregulation of the SHH pathway. Concurrently increased ECM secretion can be rescued by SHH inhibition, thus providing a putative therapeutic target. In summary, we report a human cell model of valvulogenesis that faithfully recapitulates valve disease in a dish.

https://www.ncbi.nlm.nih.gov/pubmed/31028265