PT  - JOURNAL ARTICLE
AU  - Ningbo Wu
AU  - Hongxiang Sun
AU  - Xiaoyun Zhao
AU  - Lei Chen
AU  - Yuanyuan Qi
AU  - Yuheng Han
AU  - Xianan Liu
AU  - Caixia Gao
AU  - Qun Wang
AU  - Lingjuan He
AU  - Xiaoyin Niu
AU  - Zhiduo Liu
AU  - Hua-Bing Li
AU  - Yi Arial Zeng
AU  - Manolis Roulis
AU  - Dou Liu
AU  - Zhengfeng Yang
AU  - Bin Zhou
AU  - Richard A. Flavell
AU  - Bing Su
TI  - <em>Map3k2</em>-Regulated Intestinal Stromal Cells (MRISC) Define a Distinct Sub-cryptic Stem Cell Niche for Damage Induced Wnt Agonist R-spondin1 Production
AID  - 10.1101/723221
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 723221
4099  - http://biorxiv.org/content/early/2019/10/21/723221.short
4100  - http://biorxiv.org/content/early/2019/10/21/723221.full
AB  - Intestinal stem cell propagation and differentiation are essential for rapid repair of tissue damage in the gut. While intestinal stromal cells were recently identified as key mediators of this process, the cellular and molecular mechanisms by which this diverse population induces tissue repair remains poorly understood. Here we show that Map3k2 has a colon stromal cell specific function critically required for maintenance of Lgr5+ intestinal stem cells and protection against acute intestinal damage. This Map3k2-specific function is mediated by enhancing Wnt agonist R-spondin1 production. We further reveal a unique novel cell population, named Map3k2-regulated intestinal stromal cells (MRISC), as the primary cellular source of R-spondin1 following intestinal injury. Together, our data identify a novel intestinal stem cell niche organized by MRISC, which specifically dependent on the Map3k2-signaling pathway to augment the production of Wnt agonist R-spondin1 and promote regeneration of the acutely damaged intestine.HighlightsMap3k2 protects mice from DSS-induced colitis by promoting intestinal stem cell regeneration.Map3k2-MAPK pathway cross-talks with Wnt signaling pathway via upregulation of R-spondin1.Map3k2-Regulated Intestinal Stromal Cells (MRISC) marked by co-expression of CD90, CD34 and CD81 defines a novel colonic stem cell niche.