Memory of cell shape biases stochastic fate decision-making despite mitotic rounding

Takashi Akanuma (), Cong Chen, Tetsuo Sato, Roeland M. H. Merks and Thomas N. Sato ()
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Takashi Akanuma: The Thomas N. Sato BioMEC-X Laboratories, Advanced Telecommunications Research Institute International (ATR), Hikaridai 2-2-2
Cong Chen: Centrum Wiskunde & Informatica, Life Sciences Group, Science Park 123, 1098 XG
Tetsuo Sato: The Thomas N. Sato BioMEC-X Laboratories, Advanced Telecommunications Research Institute International (ATR), Hikaridai 2-2-2
Roeland M. H. Merks: Centrum Wiskunde & Informatica, Life Sciences Group, Science Park 123, 1098 XG
Thomas N. Sato: The Thomas N. Sato BioMEC-X Laboratories, Advanced Telecommunications Research Institute International (ATR), Hikaridai 2-2-2

Nature Communications, 2016, vol. 7, issue 1, 1-17

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms11963

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