In the intestinal epithelium, proliferated epithelial cells ascend the crypts and villi and shed at the villus tips into the gut lumen. In this study, we theoretically investigate the roles of the villi on cell turnover. We present a stochastic model that focuses on the duration over which cells migrate the shortest paths between the crypt orifices and the villus tips, where shedding cells are randomly chosen from among those older than the shortest-path cell migration times. By extending the length of the shortest path to delay cell shedding, the finger-like shape of the villus would tightly regulate shedding-cell ages compared with flat surfaces and shorter projections; the villus allows epithelial cells to shed at around the same age, which limits them from shedding early or staying in the epithelium for long periods. Computational simulations of cell dynamics agreed well with the predictions. We also examine various mechanical conditions of cells and confirm that coordinated collective cell migration supports the predictions. These results suggest the important roles of the villi in homeostatic maintenance of the small intestine, and we discuss the applicability of our approach to other tissues with collective cell movement.

中文翻译：

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肠绒毛结构有助于上皮细胞的均匀脱落

在肠上皮中，增殖的上皮细胞沿隐窝和绒毛上升，并在绒毛尖端脱落进入肠腔。在这项研究中，我们从理论上研究了绒毛对细胞更新的作用。我们提出了一个随机模型，该模型侧重于细胞在隐窝孔和绒毛尖端之间迁移最短路径的持续时间，其中脱落细胞是从那些比最短路径细胞迁移时间更早的细胞中随机选择的。通过延长最短路径的长度以延迟细胞脱落，与平面和较短的突起相比，绒毛的手指状形状将严格调节脱落细胞的年龄；绒毛允许上皮细胞在大约相同的年龄脱落，这限制了它们过早脱落或长时间停留在上皮细胞中。细胞动力学的计算模拟与预测非常吻合。我们还检查了细胞的各种机械条件，并确认协调的集体细胞迁移支持预测。这些结果表明绒毛在小肠稳态维持中的重要作用，我们讨论了我们的方法对具有集体细胞运动的其他组织的适用性。