周围微环境的信号促进肠道隆起增殖并抑制肠道隆起底部的肠道干细胞（ISCs）分化。在亚上皮支撑细胞中，深亚隆突CD81 + PDGFRAlo营养细胞可以在离体情况下有效支持ISC功能。在这里，我们显示富含CD81- PDGFRAlo小鼠间质细胞的mRNA和染色质谱与营养细胞相似，两个群体提供关键的典型Wnt配体。关键的ISC支持因子的间充质表达沿着从营养细胞到周围隆突CD81- CD55hi细胞的空间和分子连续体延伸，这些细胞在组织小球共培养中模拟营养细胞的活动。基本微环境要素的分级表达不是细胞自主的，而是由距离骨形成蛋白（BMP）分泌PDGFRAhi肌成纤维细胞聚集的距离所决定。BMP信号抑制高隆起层附近PDGFRAlo细胞的ISC营养基因;在靠近和低于隆突基底的间质细胞中，包括营养细胞，该抑制得到解除。因此，细胞间距是自组织和极性ISC微环境的基础。 版权所有©2023 Elsevier Inc.。保留所有权利。

Signals from the surrounding niche drive proliferation and suppress differentiation of intestinal stem cells (ISCs) at the bottom of intestinal crypts. Among sub-epithelial support cells, deep sub-cryptal CD81+ PDGFRAlo trophocytes capably sustain ISC functions ex vivo. Here, we show that mRNA and chromatin profiles of abundant CD81- PDGFRAlo mouse stromal cells resemble those of trophocytes and that both populations provide crucial canonical Wnt ligands. Mesenchymal expression of key ISC-supportive factors extends along a spatial and molecular continuum from trophocytes into peri-cryptal CD81- CD55hi cells, which mimic trophocyte activity in organoid co-cultures. Graded expression of essential niche factors is not cell-autonomous but dictated by the distance from bone morphogenetic protein (BMP)-secreting PDGFRAhi myofibroblast aggregates. BMP signaling inhibits ISC-trophic genes in PDGFRAlo cells near high crypt tiers; that suppression is relieved in stromal cells near and below the crypt base, including trophocytes. Cell distances thus underlie a self-organized and polar ISC niche.Copyright © 2023 Elsevier Inc. All rights reserved.