NDLI: $CD34^{+}$ mesenchymal cells are a major component of the intestinal stem cells niche at homeostasis and after injury

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nigro, Giulia Dulauroy, Sophie Eberl, Gérard Jacob, Jean-marie Peduto, Lucie Sansonetti, Philippe J. Stzepourginski, Igor
Description	Author Affiliation: Stzepourginski I ( Unité Stroma, Inflammation & Tissue Repair, Institut Pasteur, 75724 Paris, France.); Nigro G ( Unité Microenvironment & Immunity, Institut Pasteur, 75724 Paris, France.); Jacob JM ( INSERM U1224, 75724 Paris, France.); Dulauroy S ( Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 75724 Paris, France.); Sansonetti PJ ( INSERM U1202, 75724 Paris, France.); Eberl G ( Unité Stroma, Inflammation & Tissue Repair, Institut Pasteur, 75724 Paris, France.); Peduto L ( INSERM U1224, 75724 Paris, France.);
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.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	4
Volume Number	114
Language	English
Publisher	National Academy of Sciences
Publisher Date	2017-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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