2026-07-21T11:39:01Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/75412024-10-31T11:56:29Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
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
funder
Fondation Leducq
funder
Fondation pour la recherche médicale (Francia)
funder
National Institutes of Health (Estados Unidos)
funder
NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos)
funder
American Heart Association
funder
National Science Foundation (Estados Unidos)
funder
Ministère de la recherche et de l’éducation (Francia)
funder
California Institute for Regenerative Medicine
2019-05-07T07:47:32Z
2019-05-07T07:47:32Z
2019
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
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.
eng
Human pre-valvular endocardial cells derived from pluripotent stem cells recapitulate cardiac pathophysiological valvulogenesis
journal article
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