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

Tui Neri, Emilye Hiriart, Patrick P. van Vliet, Emilie Faure, Russell A. Norris, Batoul Farhat, Bernd Jagla, Julie Lefrancois, Yukiko Sugi, Thomas Moore-Morris, Stéphane Zaffran, Randolph S. Faustino, Alexander C. Zambon, Jean-Pierre Desvignes, David Salgado, Robert A. Levine, Jose Luis Pompa, André Terzic, Sylvia M. Evans, Roger Markwald and Michel Pucéat ()
Additional contact information
Tui Neri: Aix-Marseille University
Emilye Hiriart: Aix-Marseille University
Patrick P. van Vliet: University of California San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences
Emilie Faure: Aix-Marseille University
Russell A. Norris: Medical University of South Carolina
Batoul Farhat: Aix-Marseille University
Bernd Jagla: Institut Pasteur - Cytometry and Biomarkers Unit of Technology and Service, Center for Translational Science and Bioinformatics and Biostatistics Hub – C3BI, USR, 3756 IP CNRS
Julie Lefrancois: Aix-Marseille University
Yukiko Sugi: Medical University of South Carolina
Thomas Moore-Morris: Aix-Marseille University
Stéphane Zaffran: Aix-Marseille University
Randolph S. Faustino: Center for Regenerative Medicine, Mayo Clinic
Alexander C. Zambon: Keck Graduate Institute
Jean-Pierre Desvignes: Aix-Marseille University
David Salgado: Aix-Marseille University
Robert A. Levine: Harvard Medical School, Massachusetts General Hospital
Jose Luis Pompa: Intercellular Signaling in Cardiovascular Development & Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
André Terzic: Center for Regenerative Medicine, Mayo Clinic
Sylvia M. Evans: University of California San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences
Roger Markwald: Medical University of South Carolina
Michel Pucéat: Aix-Marseille University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-09459-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09459-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-09459-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().