小柯机器人

美国霍华德休斯医学院Elaine Fuchs和Dana Pe’er研究组合作发现，淋巴管是调节肠道干细胞(ISCs)活动的信号中枢。相关论文发表在2022年6月20日出版的《细胞—干细胞》杂志上。

他们报告了与 ISC 密切相关的肠隐窝底部的淋巴网络。利用体内功能丧失和淋巴管-类器官共培养，他们发现隐窝淋巴管维持 ISC 并抑制其早熟分化。将单细胞和空间转录组学配对，他们应用贝叶斯棱镜对空间特征内的表达进行去卷积，并开发 SpaceFold 以在高分辨率下稳健地绘制生态位图，将淋巴管作为一般隐窝和 ISC 的中央信号枢纽。他们将 WNT 信号因子（WNT2、R-SPONDIN-3）和迄今为止未被重视的细胞外基质蛋白 REELIN， 确定为直接控制 ISC 再生潜力的隐窝淋巴信号。

据悉，屏障上皮依赖于常驻干细胞进行体内平衡、防御和修复。ISC对其局部微环境作出反应，以满足对组织更新的持续需求。这些生态位和潜在通信途径的复杂性尚不完全清楚。

附：英文原文

Title: Lymphatics act as a signaling hub to regulate intestinal stem cell activity

Author: Rachel E. Niec, Tinyi Chu, Marina Schernthanner, Shiri Gur-Cohen, Lynette Hidalgo, Hilda Amalia Pasolli, Kathleen A. Luckett, Zhong Wang, Sohni R. Bhalla, Francesco Cambuli, Raghu P. Kataru, Karuna Ganesh, Babak J. Mehrara, Dana Pe’er, Elaine Fuchs

Issue&Volume: 2022-06-20

Abstract: Barrier epithelia depend upon resident stem cells for homeostasis, defense, and repair.Epithelial stem cells of small and large intestines (ISCs) respond to their localmicroenvironments (niches) to fulfill a continuous demand for tissue turnover. Thecomplexity of these niches and underlying communication pathways are not fully known.Here, we report a lymphatic network at the intestinal crypt base that intimately associateswith ISCs. Employing in vivo loss of function and lymphatic:organoid cocultures, we show that crypt lymphaticsmaintain ISCs and inhibit their precocious differentiation. Pairing single-cell andspatial transcriptomics, we apply BayesPrism to deconvolve expression within spatialfeatures and develop SpaceFold to robustly map the niche at high resolution, exposinglymphatics as a central signaling hub for the crypt in general and ISCs in particular.We identify WNT-signaling factors (WNT2, R-SPONDIN-3) and a hitherto unappreciated extracellular matrix protein, REELIN, as crypt lymphatic signals that directly governthe regenerative potential of ISCs.

DOI: 10.1016/j.stem.2022.05.007

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00207-7

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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