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. 2021 Apr;592(7855):606-610.
doi: 10.1038/s41586-021-03283-y. Epub 2021 Mar 3.

MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche

Ningbo Wu #  1   2 , Hongxiang Sun #  1   2 , Xiaoyun Zhao  1   2 , Yao Zhang  1   3 , Jianmei Tan  1   2 , Yuanyuan Qi  1 , Qun Wang  1 , Melissa Ng  4 , Zhaoyuan Liu  1   2 , Lingjuan He  5 , Xiaoyin Niu  1 , Lei Chen  1   2   6 , Zhiduo Liu  1   2 , Hua-Bing Li  1   2   7 , Yi Arial Zeng  5 , Manolis Roulis  8 , Dou Liu  8 , Jinke Cheng  9 , Bin Zhou  5 , Lai Guan Ng  4 , Duowu Zou  3 , Youqiong Ye  1   2   7 , Richard A Flavell  7   8 , Florent Ginhoux  1   4   10 , Bing Su  11   12   13   14   15
Affiliations

MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche

Ningbo Wu et al. Nature. 2021 Apr.

Abstract

Intestinal stromal cells are known to modulate the propagation and differentiation of intestinal stem cells1,2. However, the precise cellular and molecular mechanisms by which this diverse stromal cell population maintains tissue homeostasis and repair are poorly understood. Here we describe a subset of intestinal stromal cells, named MAP3K2-regulated intestinal stromal cells (MRISCs), and show that they are the primary cellular source of the WNT agonist R-spondin 1 following intestinal injury in mice. MRISCs, which are epigenetically and transcriptomically distinct from subsets of intestinal stromal cells that have previously been reported3-6, are strategically localized at the bases of colon crypts, and function to maintain LGR5+ intestinal stem cells and protect against acute intestinal damage through enhanced R-spondin 1 production. Mechanistically, this MAP3K2 specific function is mediated by a previously unknown reactive oxygen species (ROS)-MAP3K2-ERK5-KLF2 axis to enhance production of R-spondin 1. Our results identify MRISCs as a key component of an intestinal stem cell niche that specifically depends on MAP3K2 to augment WNT signalling for the regeneration of damaged intestine.

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References

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