Memory of cell shape biases stochastic fate decision-making despite mitotic rounding.
Memory of cell shape biases stochastic fate decision-making despite mitotic rounding.
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DOI：
10.1038/ncomms11963
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发表时间：
2016-06-28
影响因子：
16.6
通讯作者：
Sato TN
中科院分区：
文献类型：
--
作者：
Akanuma T;Chen C;Sato T;Merks RM;Sato TN
细胞形状影响功能，当前模型表明这种形状效应是暂时的。然而，细胞会动态改变其形状，因此，关键问题是即使在原始形状丢失后，形状信息是否仍然对未来的细胞功能产生影响。我们通过整合实验和计算方法来解决这个问题。不对称细胞命运决策及其实时形状操纵的定量实时成像表明，尽管有丝分裂四舍五入，祖细胞的细胞偏心率确实会偏向子代细胞的随机命运决策。建模和模拟表明，祖细胞偏心率指示的 Delta 蛋白的极化定位是偏差的根源。使用不同参数进行的模拟预测，Delta 分子的扩散速率和丰度会定量地影响偏差。这些预测通过物理和遗传方法进行了实验验证，表明细胞利用本文报道的机制来根据其过去的形状影响其未来的命运，尽管动态形状发生变化。 细胞形状影响功能，但在有丝分裂细胞变圆期间，原始形状会丢失。在这里，作者结合定量实时成像、遗传操作和计算模拟表明，祖细胞的细胞偏心率会影响随机命运决定。
Cell shape influences function, and the current model suggests that such shape effect is transient. However, cells dynamically change their shapes, thus, the critical question is whether shape information remains influential on future cell function even after the original shape is lost. We address this question by integrating experimental and computational approaches. Quantitative live imaging of asymmetric cell-fate decision-making and their live shape manipulation demonstrates that cellular eccentricity of progenitor cell indeed biases stochastic fate decisions of daughter cells despite mitotic rounding. Modelling and simulation indicates that polarized localization of Delta protein instructs by the progenitor eccentricity is an origin of the bias. Simulation with varying parameters predicts that diffusion rate and abundance of Delta molecules quantitatively influence the bias. These predictions are experimentally validated by physical and genetic methods, showing that cells exploit a mechanism reported herein to influence their future fates based on their past shape despite dynamic shape changes. Cell shape influences function but during mitotic cell rounding the original shape is lost. Here the authors show that the cellular eccentricity of progenitor cell biases stochastic fate-decisions using a combination of quantitative live imaging, genetic manipulations and computational simulations.