During development, cell types differentiate from multilineage precursors in a process in which expression of mutually exclusive genes defining a particular cell fate is regulated by the underlying gene regulatory networks. Commonly, the decision to adopt one of two fates has been considered to result from stochastic fluctuations in gene expression and/or external signalling input. However, key questions remain around how appropriate timing of differentiation and correct proportions of different cell types are achieved, and how they can be recovered upon perturbation. Aneta Koseska and colleagues take a theoretical approach to addressing these questions. They consider a situation in which a dividing multilineage-primed cell can adopt two alternative fates based on the dynamics of the intercell-communication network. Simulations demonstrate that initially cells remain in the multilineage state, but the symmetry is broken when the growing population reaches a critical size, differentiating in cell types with defined proportions. These proportions can be further reliably recovered upon perturbation, i.e. removal of one cell type. They thus propose that robust cell fate proportioning and active maintenance relies on a population level cell-cell communication mechanism rather than individual cell stochasticity, and highlight the importance of cell proliferation in defining the differentiation timing.
Coupling critical population size with robust cell fate choice
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Coupling critical population size with robust cell fate choice. Development 1 February 2021; 148 (3): e148_e0303. doi:
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