The mechanism of shape-dependent stochastic asymmetric cell division

细胞间的变异越来越被认为是生物系统的一个组成部分。在这个项目中，我们探索了细胞形状的差异如何影响未来细胞行为的决定。在斑马鱼胚胎中，常见的V2祖细胞可产生V2a和V2b两种V2中间神经元。有研究认为V2祖细胞沿准随机方向分裂，分裂时不存在细胞命运偏差。然而，我们发现V2祖细胞的不同形状不仅与细胞分裂方向有关，而且与二元细胞的命运决定有一定的概率关系。我们还建立了形状相关随机V2细胞不对称分裂的抽象模型。我们通过计算机数学模拟分析了该模型，并通过操作斑马鱼胚胎对其进行了检验。我们的跨学科方法揭示了形状依赖的随机不对称细胞分裂的设计原则。

Cell-to-cell variability is increasingly appreciated as an integral part of biological systems. In this project, we explored how difference in cell shape affects the determination of future cell behavior. In zebrafish embryos, two kinds of V2 interneurons, V2a and V2b are generated from common V2 progenitor cells. It has been suggested that V2 progenitor cells divide along quasi-random directions and there is no cell fate bias at the time of cell division. However we found that varied shapes of V2 progenitor cells are coupled not only to the cell division orientation but also to the binary cell fate determination in a probabilistic manner. We also established an abstract model for shape-dependent stochastic V2 cells' asymmetric division. We analyzed this model by mathematical simulation in silico, and inspected it by manipulating the zebrafish embryos. Our interdisciplinary approach revealed the design principle for the shape-dependent stochastic asymmetric cell division.