Stromal regulation of skin homeostasis, defense and repair
Responsable du Stage :Lucie PEDUTO
Tél : 01 44 38 94 27 E-mail: firstname.lastname@example.org
Résumé du Projet de Stage
Barrier surfaces such as the skin are exposed constantly to the external environment, exposing them to infections and injuries. Barrier tissues are therefore equipped with various populations to ensure protection from pathogens, promote repair upon injury and maintain tissue homeostasis. These functions are ensured by a complex crosstalk between epithelial cells, tissue stem cells, immune cells, and several populations of stromal cells including myofibroblasts, mesenchymal cells, fibroblasts and pericytes. Stromal cells are essential for the proper functioning of blood vessels, to build a niche for tissue stem cells and to ensure immune homeostasis. Overactivation of stromal cells is implicated in a number of pathologies including chronic inflammatory diseases, autoimmune diseases, allergic diseases and poor tissue regeneration, yet how stromal cells get dysregulated is still poorly understood. Here, we want to understand how stromal cells sense their environment to maintain tissue homeostasis and ensure efficient responses to injury. To go beyond the state-of-the-art, we will perform phenotypic and transcriptomic based screens to identify stromal subsets and genes that regulate innate immunity and repair responses in conditions of activation and injury, building on existing data obtained in the lab. By using imaging, genetic lineage tracing, cellular approaches and unique mouse models our lab has generated, we expect to clarify how stromal cells adapt, sense and respond to the skin microenvironment, thereby ensuring tissue homeostasis and efficient repair responses. The student will be part of a team routinely using molecular biology, flow cytometry, imaging, genetic models and transcriptomic approaches to investigate the role of stromal cells in tissue homeostasis, immunity and disease pathogenesis including cancer and metabolic diseases
– Jacob JM, Di Carlo SE, Stzepourginski I, Lepelletier A, Ndiaye PD, Varet H, …, Nigro G, Peduto L. 2022. PDGFRα-induced stromal maturation is required to restrain postnatal intestinal epithelial stemness and promote defense mechanisms. Cell Stem Cell, 29(5): 856-868.
– Benabid A, Peduto L. 2020. Mesenchymal perivascular cells in immunity and disease. Curr Opin Immunol 64 :50-55.
– Di Carlo S, Peduto L. 2018. The perivascular origin of pathological fibroblasts. JCI review series on Fibrosis. J Clin Invest, 128(1):54-63.
– Stzepourginski I, Nigro G, Jacob JM, Dulauroy S, Sansonetti PJ, Eberl G, Peduto L. 2017. CD34+ mesenchymal cells are a major component of the intestinal stem cells niche at homeostasis and after injury. PNAS, 114(4): E506-E513.
– Dulauroy S, Di Carlo SE, Vives FL, Eberl G, and Peduto L. 2012. Lineage tracing and genetic ablation of ADAM12(+) perivascular cells identify a major source of profibrotic cells during acute tissue injury. Nature Medicine, 18(8): 1262-1270.
Ce projet s’inscrit-il dans la perspective d’une thèse :
si oui type de financement prévu : Bourse ministère/ autres bourses
Ecole Doctorale de rattachement : BioSPC ED 562
Intitulé de l’Unité : Stroma, inflammation & Tissue Repair
Equipe d’Accueil : Stroma, inflammation & Tissue Repair
Nom du Responsable de l’Unité :Lucie PEDUTO
Nom du Responsable de l’Équipe : Lucie PEDUTO
Adresse :INSTITUT PASTEUR, 25 rue du Docteur Roux, 75015 Paris