title: CD34+ mesenchymal cells are a major component of the intestinal stem cells niche at homeostasis and after injury.
abstract: The intestinal epithelium is continuously renewed by intestinal epithelial stem cells (IESCs) positioned at the base of each crypt. Mesenchymal-derived factors are essential to maintain IESCs; however, the cellular composition and development of such mesenchymal niche remains unclear. Here, we identify pericryptal CD34+Gp38+αSMA-mesenchymal cells closely associated with Lgr5+IESCs. We demonstrate that CD34+Gp38+cells are the major intestinal producers of the niche factors Wnt2b, Gremlin1, and R-spondin1, and are sufficient to promote maintenance of Lgr5+IESCs in intestinal organoids, an effect mainly mediated by Gremlin1. CD34+Gp38+cells develop after birth in the intestinal submucosa and expand around the crypts during the third week of life in mice, independently of the microbiota. We further show that pericryptal CD34+gp38+cells are rapidly activated by intestinal injury, up-regulating niche factors Gremlin1 and R-spondin1 as well as chemokines, proinflammatory cytokines, and growth factors with key roles in gut immunity and tissue repair, including IL-7, Ccl2, Ptgs2, and Amphiregulin. Our results indicate that CD34+Gp38+mesenchymal cells are programmed to develop in the intestine after birth to constitute a specialized microenvironment that maintains IESCs at homeostasis and contribute to intestinal inflammation and repair after injury.
authors.affiliation: Unité Stroma, Inflammation & Tissue Repair, Institut Pasteur, 75724 Paris, France.|Unité Microenvironment & Immunity, Institut Pasteur, 75724 Paris, France.|INSERM U1224, 75724 Paris, France.
authors.forename: Igor
authors.initials: I
authors.lastname: Stzepourginski
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75724 Paris, France.|INSERM U1202, 75724 Paris, France.
authors.forename: Giulia
authors.initials: G
authors.lastname: Nigro
authors.affiliation: Unité Stroma, Inflammation & Tissue Repair, Institut Pasteur, 75724 Paris, France.|INSERM U1224, 75724 Paris, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Jacob
authors.affiliation: Unité Microenvironment & Immunity, Institut Pasteur, 75724 Paris, France.|INSERM U1224, 75724 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Dulauroy
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75724 Paris, France; lucie.peduto@pasteur.fr philippe.sansonetti@pasteur.fr.|INSERM U1202, 75724 Paris, France.|Chaire de Microbiologie et Maladies Infectieuses, Collège de France, 75231 Paris, France.
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
authors.affiliation: Unité Microenvironment & Immunity, Institut Pasteur, 75724 Paris, France.|INSERM U1224, 75724 Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Eberl
authors.affiliation: Unité Stroma, Inflammation & Tissue Repair, Institut Pasteur, 75724 Paris, France; lucie.peduto@pasteur.fr philippe.sansonetti@pasteur.fr.|INSERM U1224, 75724 Paris, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Peduto
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D006706:Homeostasis; D007413:Intestinal Mucosa / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D055153:Stem Cell Niche
chemical_list: D018952:Antigens, CD34; D016264:Dextran Sulfate
keywords: CD34; inflammation; intestinal stem cells; mesenchymal niche