Deciphering the Role of Fluctuation Dependent Intercellular Communication in Neural Stem Cell Development.

Neural stem cells (NPCs) efficiently communicate in an intercellular manner to govern specific cell fate decisions during the developmental process despite withstanding the fluctuating cellular environment. How these fluctuations from diverse origins functionally affect the precise cell fate decision making remains elusive. By taking a stochastic mathematical modeling approach, we unravel that the transcriptional variability arising within an NPC population due to intermittent cell cycle events significantly influences the neuron to NPC ratio during development. Our model proficiently quantifies the impact of different sources of heterogeneities in maintaining an exact neuron to NPC ratio and predicts plausible experimental ways to fine-tune the development of NPCs. In the future, these modeling insights may lead to better therapeutic avenues to regenerate neurons from NPCs.