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Lebas, M.* ; Chinigò, G.* ; Courmont, E.* ; Bettaieb, L.* ; Machmouchi, A.* ; Goveia, J.* ; Beatovic, A.* ; Van Kerckhove, J.* ; Robil, C.* ; Angulo, F.S.* ; Vedelago, M.* ; Errerd, A.* ; Treps, L.* ; Gao, V.* ; Delgado De La Herran, H.C. ; Mayeuf-Louchart, A.* ; L'homme, L.* ; Chamlali, M.* ; Dejos, C.* ; Gouyer, V.* ; Garikipati, V.N.S.* ; Tomar, D.* ; Yin, H.* ; Fukui, H.* ; Vinckier, S.* ; Stolte, A.* ; Conradi, L.C.* ; Infanti, F.* ; Lemonnier, L.* ; Zeisberg, E.M.* ; Luo, Y.* ; Lin, L.* ; Desseyn, J.L.* ; Pickering, J.W.* ; Kishore, R.* ; Madesh, M.* ; Dombrowicz, D.* ; Perocchi, F. ; Staels, B.* ; Pla, A.F.* ; Gkika, D.* ; Cantelmo, A.R.*

Integrated single-cell RNA-seq analysis reveals mitochondrial calcium signaling as a modulator of endothelial-to-mesenchymal transition.

Sci. Adv. 10:eadp6182 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Endothelial cells (ECs) are highly plastic, capable of differentiating into various cell types. Endothelial-to-mesenchymal transition (EndMT) is crucial during embryonic development and contributes substantially to vascular dysfunction in many cardiovascular diseases (CVDs). While targeting EndMT holds therapeutic promise, understanding its mechanisms and modulating its pathways remain challenging. Using single-cell RNA sequencing on three in vitro EndMT models, we identified conserved gene signatures. We validated original regulators in vitro and in vivo during embryonic heart development and peripheral artery disease. EndMT induction led to global expression changes in all EC subtypes rather than in mesenchymal clusters. We identified mitochondrial calcium uptake as a key driver of EndMT; inhibiting mitochondrial calcium uniporter (MCU) prevented EndMT in vitro, and conditional Mcu deletion in ECs blocked mesenchymal activation in a hind limb ischemia model. Tissues from patients with critical limb ischemia with EndMT features exhibited significantly elevated endothelial MCU. These findings highlight MCU as a regulator of EndMT and a potential therapeutic target.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Endoplasmic-reticulum; Valve Development; Contributes; Promotes; Differentiation; Heterogeneity; Pathogenesis; Dysfunction; Mechanisms; Expression
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Zeitschrift Science Advances
Quellenangaben Band: 10, Heft: 32, Seiten: , Artikelnummer: eadp6182 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort Washington, DC [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502295-001
Förderungen La Ligue Contre le Cancer, Septentrion
Canadian Institutes of Health Research
University of Torino
Universite de Lille
Institute Pasteur de Lille/ Region Hauts-de-France
ITMO Cancer of Aviesan
Agence Nationale de la Recherche Investissements d'avenir
La Ligue Contre le Cancer (Pas de Calais)
Contrat de Plan Etat-Region CPER Cancer
National Institutes of Health
Cancerople Nord-Ouest-AAP Projets Emergents
France Berkley Fund
Institut Universitaire de France (IUF)
ExNet-0041-Phase2-3 ("SyNergy-HMGU") through the Initiative and Network Fund of the Helmholtz Association
Munich Center for Systems Neurology (SyNergy)
San Antonio Partnership for Precision Therapeutics (SAPPT)
DOD/DHP-CDMRP
ITMO Cancer of Aviesan by Inserm
DOI 10.1126/sciadv.adp6182
WOS ID 001305398300003
Scopus ID 85201064349
PubMed ID 39121218
Erfassungsdatum 2024-09-27
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