Transcriptional network dynamics in early T cell development

Multipotent blood progenitors begin T cell development in the thymus, activating a multistep gene regulatory network. This review explores how the dynamic interplay between Notch signals, Notch-induced factors, and progenitor-associated factors control T-development progression by synergizing and opposing each other's action. The rate at which cells enter the T cell pathway depends not only on the immigration of hematopoietic precursors into the strong Notch signaling environment of the thymus but also on the kinetics with which each individual precursor cell reaches T-lineage commitment once it arrives. Notch triggers a complex, multistep gene regulatory network in the cells in which the steps are stereotyped but the transition speeds between steps are variable. Progenitor-associated transcription factors delay T-lineage differentiation even while Notch-induced transcription factors within the same cells push differentiation forward. Progress depends on regulator cross-repression, on breaching chromatin barriers, and on shifting, competitive collaborations between stage-specific and stably expressed transcription factors, as reviewed here.