Title :

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

Author(s) :

Lebas, Mathilde [Auteur]
Institut Pasteur de Lille
Chinigò, G. [Auteur]
Courmont, Evan [Auteur]
Institut Pasteur de Lille
Bettaieb, Louay [Auteur]
Institut Pasteur de Lille
Machmouchi, Amani [Auteur]
Institut Pasteur de Lille
Goveia, J. [Auteur]
Beatovic, A. [Auteur]
van Kerckhove, J. [Auteur]
Robil, Cyril [Auteur]
Institut Pasteur de Lille
Angulo, F. S. [Auteur]
Vedelago, M. [Auteur]
Errerd, A. [Auteur]
Treps, L. [Auteur]
Gao, Vance [Auteur]
Institut Pasteur de Lille
Delgado de la Herrán, H. C. [Auteur]
Mayeuf-Louchart, Alicia [Auteur]
Institut Pasteur de Lille
L'Homme, Laurent [Auteur]
Institut Pasteur de Lille
Chamlali, M. [Auteur]
Dejos, C. [Auteur]
Gouyer, Valerie [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Garikipati, V. N. S. [Auteur]
Tomar, D. [Auteur]
Yin, H. [Auteur]
Fukui, H. [Auteur]
Vinckier, S. [Auteur]
Stolte, A. [Auteur]
Conradi, L. C. [Auteur]
Infanti, F. [Auteur]
Lemonnier, Loic [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Zeisberg, E. [Auteur]
Luo, Y. [Auteur]
Lin, L. [Auteur]
Desseyn, Jean-Luc [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Pickering, J. [Auteur]
Kishore, R. [Auteur]
Madesh, M. [Auteur]
Dombrowicz, David [Auteur]
Institut Pasteur de Lille
Perocchi, F. [Auteur]
Staels, Bart [Auteur]
Institut Pasteur de Lille
Pla, A. F. [Auteur]
Gkika, Dimitra [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Cantelmo, Anna Rita [Auteur]
Institut Pasteur de Lille

Journal title :

Science Advances
Sci Adv

Pages :

eadp6182

Publisher :

American Association for the Advancement of Science (AAAS)

Publication date :

2024-08-18

ISSN :

2375-2548

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL