Robustness and timing of cellular differentiation through population-based symmetry breaking

Area of Science:

• Developmental Biology
• Systems Biology
• Cellular Dynamics

Background:

• Cell differentiation typically transitions cells from a primed state to specific types, marked by unique genetic markers.
• Classical models explain differentiation via single-cell multistability, relying on pre-existing cell differences for cell-type proportioning.

Purpose of the Study:

• To propose a novel dynamical mechanism for cell differentiation based on collective cell-cell communication.
• To investigate how cell populations collectively maintain differentiated cell types and robust proportions.

Main Methods:

• Modeling cell-cell communication as a novel inhomogeneous state of a coupled system.
• Analyzing the dynamics of differentiation triggered by cell number increase in growing populations.
• Investigating the stability and recovery of differentiated cell types under perturbation.

Main Results:

• Cell types emerge and are maintained collectively through cell-cell communication, forming an inhomogeneous state.
• Differentiation is triggered by population growth and organization before a symmetry-breaking bifurcation.
• The collective mechanism ensures robust cell-type proportioning and reliable recovery post-perturbation.

Conclusions:

• Cell differentiation can emerge from the cooperative behavior of growing cell populations, challenging single-cell multistability models.
• Cell-cell communication is a key driver for generating and maintaining differentiated cell types in robust proportions.
• This collective dynamical mechanism provides a new framework for understanding developmental timing and cell fate decisions.