Genetic analysis of differentiation of T-helper lymphocytes

TL;DR

This paper presents a system dynamics model of T-helper cell differentiation, revealing how gene expression and system stability influence cell potential and cytokine oscillations.

Contribution

It introduces a novel dynamic model simulating T-helper cell differentiation based on gene expression and stability analysis.

Findings

Cell differentiation potential exists at unstable equilibrium points.

Stable equilibrium indicates loss of differentiation potential.

Expression time lag causes cytokine secretion oscillations.

Abstract

In the human immune system, T-helper cells are able to differentiate into two lymphocyte subsets: Th1 and Th2. The intracellular signaling pathways of differentiation form a dynamic regulation network by secreting distinctive types of cytokines, while differentiation is regulated by two major gene loci: T-bet and GATA-3. We developed a system dynamics model to simulate the differentiation and re-differentiation process of T-helper cells, based on gene expression levels of T-bet and GATA-3 during differentiation of these cells. We arrived at three ultimate states of the model and came to the conclusion that cell differentiation potential exists as long as the system dynamics is at an unstable equilibrium point; the T-helper cells will no longer have the potential of differentiation when the model reaches a stable equilibrium point. In addition, the time lag caused by expression of transcription factors can lead to oscillations in the secretion of cytokines during differentiation.