Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
Elife. 2018 Jun 13;7:e36739. doi: 10.7554/eLife.36739.
Cell division is essential to expand, shape, and replenish epithelia. In the adult small intestine, cells from a common progenitor intermix with other lineages, whereas cell progeny in many other epithelia form contiguous patches. The mechanisms that generate these distinct patterns of progeny are poorly understood. Using light sheet and confocal imaging of intestinal organoids, we show that lineages intersperse during cytokinesis, when elongated interphase cells insert between apically displaced daughters. Reducing the cellular aspect ratio to minimize the height difference between interphase and mitotic cells disrupts interspersion, producing contiguous patches. Cellular aspect ratio is similarly a key parameter for division-coupled interspersion in the early mouse embryo, suggesting that this physical mechanism for patterning progeny may pertain to many mammalian epithelia. Our results reveal that the process of cytokinesis in elongated mammalian epithelia allows lineages to intermix and that cellular aspect ratio is a critical modulator of the progeny pattern.
细胞分裂对于上皮组织的扩张、塑形和补充至关重要。在成年小肠中，来自共同祖细胞的细胞与其他谱系混合，而在许多其他上皮组织中，细胞后代形成连续的斑块。产生这些不同的后代模式的机制还不太清楚。我们使用小肠类器官的光片和共聚焦成像技术表明，在有丝分裂过程中，当拉长的间期间期细胞插入到顶端位移的子细胞之间时，谱系会交织在一起。减少细胞纵横比以最小化间期间期和有丝分裂细胞之间的高度差会破坏交织，产生连续的斑块。细胞纵横比对于早期小鼠胚胎中的分裂偶联交织也是一个关键参数，这表明这种用于图案化后代的物理机制可能与许多哺乳动物上皮组织有关。我们的结果表明，伸长的哺乳动物上皮组织中的有丝分裂过程允许谱系混合，并且细胞纵横比是后代模式的关键调节剂。
