Cellular aspect ratio and cell division mechanics underlie the patterning of cell progeny in diverse mammalian epithelia.
Cellular aspect ratio and cell division mechanics underlie the patterning of cell progeny in diverse mammalian epithelia.
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DOI：
10.7554/elife.36739
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发表时间：
2018-06-13
期刊：
影响因子：
7.7
通讯作者：
Vale RD
中科院分区：
文献类型：
--
作者：
McKinley KL;Stuurman N;Royer LA;Schartner C;Castillo-Azofeifa D;Delling M;Klein OD;Vale RD
细胞分裂是上皮细胞扩张、成形和补充的必要条件。在成人小肠中，来自共同祖细胞的细胞与其他细胞系混合，而许多其他上皮细胞的后代形成连续的斑块。产生这些不同模式的后代的机制尚不清楚。通过对肠道类器官的光片和共聚焦成像，我们发现细胞质分裂过程中，当伸长的间期细胞插入顶端移位的子代细胞之间时，谱系是分散的。减少细胞长宽比，以尽量减少间期和有丝分裂细胞之间的高度差，破坏散布，产生连续的斑块。细胞长径比同样是早期小鼠胚胎中分裂偶联分散的关键参数，这表明这种形成后代的物理机制可能适用于许多哺乳动物上皮。我们的研究结果表明，细长哺乳动物上皮细胞的细胞质分裂过程允许谱系混合，细胞长径比是后代模式的关键调节剂。人体有一种令人印象深刻的自我更新能力，可以用新的细胞替换旧的和受损的细胞。这可能发生得很快；例如，肠道内壁大约每五天更新一次。细胞膜包含许多不同类型的细胞，它们与相邻的细胞交换重要的信号。这意味着新细胞需要占据与它们取代的细胞相似的位置，以保持肠道的工作。当现有细胞的内容加倍并分裂时，就会形成新的细胞。在许多组织中，产生的细胞并排排列。但是当肠细胞分裂时，新细胞通常会分离，最终出现在未分裂细胞的两侧。为了研究这是如何发生的，McKinley等人使用活体显微镜技术实时观察新细胞在小鼠肠道类器官（可以在体外生长的器官的微型版本）中分裂和定位。这揭示了肠细胞的形状解释了为什么新形成的细胞会分离。肠细胞的高度大于宽度，并在顶部边缘附近分裂。这使得相邻的细胞能够在新细胞分裂时挤在它们之间。进一步的实验表明，小鼠其他组织中的tall细胞也会在分裂后分离。因此，新细胞因其高度而与邻近细胞穿插的过程并不是肠道所独有的。它可能在其他哺乳动物组织中也很常见。因为实验室现在可以培育许多类型的类器官，代表不同的器官，所以进一步研究这个问题有很大的潜力。使用活体显微镜检查它们可以揭示更多关于各种组织如何生长的信息。
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. The body has an impressive ability to renew itself by replacing old and damaged cells with new ones. This can happen rapidly; for example, the lining of the intestine renews itself approximately every five days. The lining contains many different cell types, which exchange important signals with their neighbors. This means that the new cells need to occupy similar positions to the ones they are replacing to keep the intestine working. New cells form when existing cells double their contents and divide. In many tissues the resulting cells sit side-by-side. But when cells in the intestine divide, the new cells often separate, ending up on either side of a cell that did not divide. To investigate how this happens, McKinley et al. used live microscopy techniques to watch in real time as new cells divide and position themselves in mouse intestinal organoids – miniature versions of organs that can be grown outside the body. This revealed that the shape of intestinal cells explains why the newly formed cells become separated. Intestinal cells are taller than they are wide, and divide near their top edge. This enables a neighboring cell to squeeze between the new cells as they divide. Further experiments showed that tall cells in other mouse tissues also become separated after division. The process of new cells interspersing with their neighbors due to their height is therefore not unique to the intestine. It may also be common in other mammalian tissues. There is great potential for investigating this further because labs can now grow many types of organoids, representing different organs. Using live microscopy to examine them could reveal more about how various tissues grow.