Irreversibility of T-Cell Specification: Insights from Computational Modelling of a Minimal Network Architecture.

ABSTRACT:

Background/objectives

A cascade of gene activations under the control of Notch signalling is required during T-cell specification, when T-cell precursors gradually lose the potential to undertake other fates and become fully committed to the T-cell lineage. We elucidate how the gene/protein dynamics for a core transcriptional module governs this important process by computational means.

Methods

We first assembled existing knowledge about transcription factors known to be important for T-cell specification to form a minimal core module consisting of TCF-1, GATA-3, BCL11B, and PU.1 aiming at dynamical modeling. Model architecture was based on published experimental measurements of the effects on each factor when each of the others is perturbed. While several studies provided g

SUBMITTER: Manesso E 

PROVIDER: S-EPMC4995000 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature