2026-07-21T11:39:01Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/75412024-10-31T11:56:29Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Neri, Tui author Hiriart, Emilye author van Vliet, Patrick P author Faure, Emilie author Norris, Russell A author Farhat, Batoul author Jagla, Bernd author Lefrancois, Julie author Sugi, Yukiko author Moore-Morris, Thomas author Zaffran, Stéphane author Faustino, Randolph S author Zambon, Alexander C author Desvignes, Jean-Pierre author Salgado, David author Levine, Robert A author de la Pompa, Jose Luis author Terzic, André author Evans, Sylvia M author Markwald, Roger author Pucéat, Michel author 2019 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. Nat Commun. 2019; 10(1):1929 10.1038/s41467-019-09459-5 2041-1723 2041-1723 Nature communications 31028265 http://hdl.handle.net/20.500.12105/7541 Human pre-valvular endocardial cells derived from pluripotent stem cells recapitulate cardiac pathophysiological valvulogenesis