Emergent dynamics of a three-node regulatory network explain phenotypic switching and heterogeneity: a case study of Th1/Th2/Th17 cell differentiation.

ABSTRACT: Naïve helper (CD4+) T-cells can differentiate into distinct functional subsets including Th1, Th2, and Th17 phenotypes. Each of these phenotypes has a "master regulator"-T-bet (Th1), GATA3 (Th2), and RORγT (Th17)-that inhibits the other two master regulators. Such mutual repression among them at a transcriptional level can enable multistability, giving rise to six experimentally observed phenotype, Th1, Th2, Th17, hybrid Th/Th2, hybrid Th2/Th17, and hybrid Th1/Th17. However, the dynamics of switching among these phenotypes, particularly in the case of epigenetic influence, remain unclear. Here through mathematical modeling, we investigated the coupled transcription-epigenetic dynamics in a three-node mutually repressing network to elucidate how epigenetic changes mediated by any master reg

SUBMITTER: Duddu AS 

PROVIDER: S-EPMC9265159 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature