小柯机器人

上海交通大学医学院苏冰研究组发现，MAP3K2调控的肠道基质细胞可定义一种独特的干细胞微环境。2021年3月2日，《自然》杂志在线发表了这项成果。

研究人员报道了一类肠基质细胞的亚群，被命名为MAP3K2调节的肠基质细胞（MRISCs），并发现它们是小鼠肠损伤后WNT激动因子R-spondin 1的主要细胞来源。MRISCs在表观遗传学和转录组学上不同于先前报道的小肠基质细胞亚型，其策略性地定位在结肠隐窝的底部，并起维持LGR5⁺小肠干细胞的作用，并防止急性小肠损伤通过增强的R-spondin 1生产。

从机理上讲，这种MAP3K2的特定功能是由先前未知的活性氧（ROS）–MAP3K2–ERK5–KLF2信号轴介导的，从而增强R-spondin 1的产生。这些研究结果表明，MRISCs是肠道干细胞微环境的关键组成部分，它特别依赖于MAP3K2来增强WNT信号，从而再生受损的肠道。  

据悉，肠基质细胞可调节肠干细胞的增殖和分化。但是，人们对这种多样化的基质细胞群维持组织稳态和修复的具体细胞和分子机制了解甚少。

附：英文原文

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

Author: Ningbo Wu, Hongxiang Sun, Xiaoyun Zhao, Yao Zhang, Jianmei Tan, Yuanyuan Qi, Qun Wang, Melissa Ng, Zhaoyuan Liu, Lingjuan He, Xiaoyin Niu, Lei Chen, Zhiduo Liu, Hua-Bing Li, Yi Arial Zeng, Manolis Roulis, Dou Liu, Jinke Cheng, Bin Zhou, Lai Guan Ng, Duowu Zou, Youqiong Ye, Richard A. Flavell, Florent Ginhoux, Bing Su

Issue&Volume: 2021-03-03

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 reported3,4,5,6, 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.

DOI: 10.1038/s41586-021-03283-y

Source: https://www.nature.com/articles/s41586-021-03283-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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