Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi.
Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi.
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DOI：
10.1096/fj.201601002
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Pin C
中科院分区：
文献类型：
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作者：
Parker A;Maclaren OJ;Fletcher AG;Muraro D;Kreuzaler PA;Byrne HM;Maini PK;Watson AJ;Pin C
肠上皮屏障的功能完整性依赖于细胞增殖和迁移的紧密协调，不能调节这些过程会导致疾病。尚不清楚在上皮细胞的稳态更新期间，细胞增殖是否足以驱动上皮细胞迁移。也不知道如何绒毛细胞迁移时，增殖受到干扰的影响。一些报告表明，扩散和迁移可能没有关系，而其他研究支持直接关系。我们使用了基于胸腺嘧啶类似物细胞标记的细胞跟踪方法，并开发了量身定制的数学模型来量化正常条件下以及增殖减少和暂时停止时的细胞增殖和迁移。我们发现，上皮细胞迁移速度沿着绒毛耦合细胞增殖率在所有条件下的隐窝。此外，停止和恢复增殖导致绒毛上细胞迁移的同步反应。我们的结论是，细胞增殖的隐窝内的主要力量，驱动细胞迁移沿着绒毛。这种方法可用于询问肠上皮动力学，并表征参与细胞更新的过程变得解偶联的情况，包括药物治疗和疾病模型。帕克，麦克拉伦岛J.，弗莱彻，A. G.，Muraro，D.，Kreuzaler，P. A.，Byrne，H. M.，Maini，P. K.，沃森，A. J.M.，平角小肠隐窝内的细胞增殖是细胞在绒毛上迁移的主要驱动力。
The functional integrity of the intestinal epithelial barrier relies on tight coordination of cell proliferation and migration, with failure to regulate these processes resulting in disease. It is not known whether cell proliferation is sufficient to drive epithelial cell migration during homoeostatic turnover of the epithelium. Nor is it known precisely how villus cell migration is affected when proliferation is perturbed. Some reports suggest that proliferation and migration may not be related while other studies support a direct relationship. We used established cell-tracking methods based on thymine analog cell labeling and developed tailored mathematical models to quantify cell proliferation and migration under normal conditions and when proliferation is reduced and when it is temporarily halted. We found that epithelial cell migration velocities along the villi are coupled to cell proliferation rates within the crypts in all conditions. Furthermore, halting and resuming proliferation results in the synchronized response of cell migration on the villi. We conclude that cell proliferation within the crypt is the primary force that drives cell migration along the villus. This methodology can be applied to interrogate intestinal epithelial dynamics and characterize situations in which processes involved in cell turnover become uncoupled, including pharmacological treatments and disease models.—Parker, A., Maclaren, O. J., Fletcher, A. G., Muraro, D., Kreuzaler, P. A., Byrne, H. M., Maini, P. K., Watson, A. J. M., Pin, C. Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi.