Intestinal organoids capture essential features of the intestinal epithelium such as crypt folding, cellular compartmentalization and collective movements. Each of these processes and their coordination require patterned forces that are at present unknown. Here we map three-dimensional cellular forces in mouse intestinal organoids grown on soft hydrogels. We show that these organoids exhibit a non-monotonic stress distribution that defines mechanical and functional compartments. The stem cell compartment pushes the extracellular matrix and folds through apical constriction, whereas the transit amplifying zone pulls the extracellular matrix and elongates through basal constriction. The size of the stem cell compartment depends on the extracellular-matrix stiffness and endogenous cellular forces. Computational modelling reveals that crypt shape and force distribution rely on cell surface tensions following cortical actomyosin density. Finally, cells are pulled out of the crypt along a gradient of increasing tension. Our study unveils how patterned forces enable compartmentalization, folding and collective migration in the intestinal epithelium.

肠类器官捕获肠上皮细胞的基本特征，例如隐窝折叠、细胞区室化和集体运动。这些过程中的每一个及其协调都需要目前未知的模式化力量。在这里，我们绘制了在软水凝胶上生长的小鼠肠道类器官的三维细胞力。我们表明，这些类器官表现出非单调的应力分布，该分布定义了机械和功能隔间。干细胞隔室推动细胞外基质并通过顶端收缩折叠，而转运放大区拉动细胞外基质并通过基底收缩延长。干细胞区室的大小取决于细胞外基质硬度和内源性细胞力。计算模型表明，隐窝形状和力分布依赖于皮质肌动球蛋白密度后的细胞表面张力。最后，细胞沿着逐渐增加的张力梯度被拉出隐窝。我们的研究揭示了模式化的力量如何在肠上皮细胞中实现区室化、折叠和集体迁移。