Epithelial Cell Packing Induces Distinct Modes of Cell Extrusions.
Epithelial Cell Packing Induces Distinct Modes of Cell Extrusions.
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DOI：
10.1016/j.cub.2016.08.057
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发表时间：
2016-11-07
期刊：
影响因子：
--
通讯作者：
Ladoux B
中科院分区：
文献类型：
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作者：
Kocgozlu L;Saw TB;Le AP;Yow I;Shagirov M;Wong E;Mège RM;Lim CT;Toyama Y;Ladoux B
组织生长的控制是维持上皮保护屏障功能的关键，取决于细胞分裂和细胞挤出速率之间的平衡。融合上皮层内的细胞经历细胞挤出，这依赖于细胞-细胞相互作用和肌动球蛋白收缩性。尽管已经报道细胞挤出也依赖于细胞密度，但是受细胞密度严格调节的组织力学对细胞挤出的贡献仍然知之甚少。通过测量多细胞动力学和牵引力，我们表明，上皮细胞堆积密度的变化导致出现不同的细胞挤出模式。在细胞密度低的融合上皮中，细胞挤出主要由邻近非死亡细胞中基于板状伪足的爬行机制驱动，与大规模集体运动有关。随着细胞密度的增加，细胞运动被证明是放缓和超细胞肌动球蛋白电缆的形成和其在相邻细胞中的收缩的作用成为局部促进细胞挤出的优势机制。我们建议这两种不同的机制相互补充，以确保适当的细胞挤出取决于细胞环境。我们的研究提供了一个定量和强大的框架来解释细胞密度如何影响组织力学，从而调节细胞挤出机制。
The control of tissue growth, which is a key to maintain the protective barrier function of the epithelium, depends on the balance between cell division and cell extrusion rates. Cells within confluent epithelial layers undergo cell extrusion, which relies on cell-cell interactions and actomyosin contractility. Although it has been reported that cell extrusion is also dependent on cell density, the contribution of tissue mechanics, which is tightly regulated by cell density, to cell extrusion is still poorly understood. By measuring the multi-cellular dynamics and traction forces, we show that changes in epithelial packing density lead to the emergence of distinct modes of cell extrusion. In confluent epithelia with low cell density, cell extrusion is mainly driven by the lamellipodia-based crawling mechanism in the neighbor non-dying cells in connection with large-scale collective movements. As cell density increases, cell motion is shown to slow down and the role of a supra-cellular actomyosin cable formation and its contraction in the neighboring cells becomes the preponderant mechanism to locally promote cell extrusion. We propose that these two distinct mechanisms complement each other to ensure proper cell extrusion depending on the cellular environment. Our study provides a quantitative and robust framework to explain how cell density can influence tissue mechanics and in turn, regulate cell extrusion mechanism.