Cooperative regulation of cellular identity in systems with intercellular communication defects

TL;DR

This study investigates how cellular populations, specifically pancreatic beta-cells, maintain their functional identity despite intercellular communication defects, revealing that cooperative regulation reduces the likelihood of pathological states.

Contribution

It introduces a Hodgkin-Huxley based model to show how cooperative dynamics in cell populations stabilize physiological behavior even with defective intercellular channels.

Findings

Pathological behavior probability is nearly 100% in homogeneous defective populations.

Heterogeneous populations have less than 10% chance of stable pathology.

Cooperative regulation enhances population resilience against defects.

Abstract

The cooperative dynamics of cellular populations emerging from the underlying interactions determines cellular functions, and thereby their identity in tissues. Global deviations from this dynamics on the other hand reflects pathological conditions. However, how these conditions are stabilized from dis-regulation on the level of the single entities is still unclear. Here we tackle this question using generic Hodgkin-Huxley type of models that describe physiological bursting dynamics of pancreatic beta-cells, and introduce channel dis-function to mimic pathological silent dynamics. The probability for pathological behavior in beta-cell populations is $\sim100\%$ when all cell have these defects, despite the negligible size of the silent state basin of attraction for single cells. In stark contrast, in a more realistic scenario for a heterogeneous population, stabilization of the pathological state depends on the size of the sub-population which acquired the defects. However, the probability to exhibit stable pathological dynamics in this case is less than $\sim10\%$. These results therefore suggest that the physiological bursting dynamics of a population of beta-cells is cooperatively regulated, even under intercellular communication defects induced by dis-functional channels of single-cells.