Journal articles
Human pre-valvular endocardial cells derived from pluripotent stem cells recapitulate cardiac pathophysiological valvulogenesis
Tui Neri
1
Emilye Hiriart
2
Patrick P. Vliet
3
Emilie Faure
2
Russell A. Norris
4
Batoul Farhat
2
Bernd Jagla
5
Julie Lefrancois
Yukiko Sugi
4
Thomas Moore-Morris
2
Stéphane Zaffran
2
Randolph S. Faustino
6
Alexander C. Zambon
7
Jean-Pierre Desvignes
2
David Salgado
2
Robert A. Levine
8
Jose Luis Pompa
9, 10
Andre Terzic
11
Sylvia M. Evans
12, 13, 14
Roger Markwald
4
Michel Puceat
2, *
*
Corresponding author
Yukiko Sugi 4
Author
Thomas Moore-Morris 2
Author IdHAL : thomas-moore-morris ORCID : https://orcid.org/0000-0002-4611-042X
Stéphane Zaffran 2
Author IdHAL : stephane-zaffran ORCID : https://orcid.org/0000-0002-0811-418X
Randolph S. Faustino 6
Author
Alexander C. Zambon 7
Author
Jean-Pierre Desvignes 2
Author IdHAL : jean-pierre-desvignes ResearcherId : http://www.researcherid.com/rid/I-2858-2016 ORCID : https://orcid.org/0000-0003-3142-1994
David Salgado 2
Author IdHAL : david-salgado ResearcherId : http://www.researcherid.com/rid/A-1417-2014 ORCID : https://orcid.org/0000-0002-5905-3591
Robert A. Levine 8
Author
Jose Luis de La Pompa 9, 10
Author
Andre Terzic 11
Author
Sylvia M. Evans 12, 13, 14
Author
Roger Markwald 4
Author
Michel Puceat 2
Correspondent author IdHAL : michel-puceat ResearcherId : http://www.researcherid.com/rid/R-6140-2017 ORCID : https://orcid.org/0000-0001-9055-7563
1
I-STEM - Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (GENETHON 1, rue de l'internationale BP 118 94004 EVRY CEDEX - France)
- UEVE - Université d'Évry-Val-d'Essonne (Boulevard François Mitterrand 91025 Evry Cedex - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U861 (101, rue de Tolbiac, 75013 Paris - France)
- Généthon (1 rue de l’Internationale, 9100 Evry - France)
2
MMG - Marseille medical genetics - Centre de génétique médicale de Marseille (Faculté de Médecine - Timone
27, boulevard Jean Moulin
13385 Marseille cedex 5 - France)
- AMU - Aix Marseille Université : UMR_S1251 (Aix-Marseille Université Jardins du Pharo 58 Boulevard Charles Livon 13284 Marseille cedex 7 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : UMR_S1251 (101, rue de Tolbiac, 75013 Paris - France)
3
UC San Diego - University of California [San Diego] (9500 Gilman Dr., La Jolla, CA 92093 USA - United States)
- University of California (United States)
4
MUSC - Medical University of South Carolina [Charleston] (171 Ashley Avenue, Charleston SC 29425 - United States)
5
C3BI - Centre de Bioinformatique, Biostatistique et Biologie Intégrative (25-28 rue du docteur Roux, 75724 Paris cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- CNRS - Centre National de la Recherche Scientifique : USR3756 (France)
6
Mayo Clinic [Rochester] (200 First St. SW
Rochester, MN 55905 - United States)
7
KGI - Keck Graduate Institute [Claremont, Californie] (535 Watson Drive -
Claremont, CA 91711 - United States)
8
Massachusetts General Hospital [Boston] (55 Fruit Street
Boston, MA 02114 - United States)
9
CNIC - Centro Nacional de Investigaciones Cardiovasculares Carlos III [Madrid, Spain] (Calle de Melchor Fernández Almagro, 3, 28029 Madrid, Espagne - Spain)
- ISC - Instituto de Salud Carlos III [Madrid] ( Carretera de Majadahonda - Pozuelo, 28220 Majadahonda, Madrid, Espagne - Spain)
10
ISC - Instituto de Salud Carlos III [Madrid] ( Carretera de Majadahonda - Pozuelo, 28220 Majadahonda, Madrid, Espagne - Spain)
11
Division of Cardiovascular Diseases (Departments of Medicine, Molecular Pharmacology and Expermental Therapeutics, Rochester - United States)
- Mayo Clinic College of Medicine (France)
12
Skaggs School of Pharmacy and Pharmaceutical Sciences [San Diego] (9500 Gilman Dr. La Jolla, San Diego CA 92093 - United States)
- UC San Diego - University of California [San Diego] (9500 Gilman Dr., La Jolla, CA 92093 USA - United States)
- University of California (United States)
13
Department of Medicine [San Diego] (9500 Gilman Drive
La Jolla San Diego CA 92093 USA - United States)
- UC San Diego - University of California [San Diego] (9500 Gilman Dr., La Jolla, CA 92093 USA - United States)
- University of California (United States)
14
Department of Pharmacology [La Jolla, CA, USA] (La Jolla, 92093, CA. - United States)
- UC San Diego - University of California [San Diego] (9500 Gilman Dr., La Jolla, CA 92093 USA - United States)
- University of California (United States)
Abstract : 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.
Keywords :
Developmental biology
Disease model
Document type :
Journal articles
Domain :
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https://hal-amu.archives-ouvertes.fr/hal-02461454
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Submitted on : Tuesday, March 24, 2020 - 4:39:36 PM
Last modification on : Saturday, July 3, 2021 - 12:11:54 AM
Contributor : Valérie Gall <>
Submitted on : Tuesday, March 24, 2020 - 4:39:36 PM
Last modification on : Saturday, July 3, 2021 - 12:11:54 AM
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Distributed under a Creative Commons Attribution 4.0 International License
Identifiers
- HAL Id : hal-02461454, version 1
- DOI : 10.1038/s41467-019-09459-5
- PUBMED : 31028265
- PUBMEDCENTRAL : PMC6486645
Citation
Tui Neri, Emilye Hiriart, Patrick P. Vliet, Emilie Faure, Russell A. Norris, et al.. Human pre-valvular endocardial cells derived from pluripotent stem cells recapitulate cardiac pathophysiological valvulogenesis. Nature Communications, Nature Publishing Group, 2019, 10, pp.1929. ⟨10.1038/s41467-019-09459-5⟩. ⟨hal-02461454⟩
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