Regulatory factors for initial T lymphocyte lineage specification

Initiation of T lymphocyte development depends on balanced regulatory inputs from multiple essential transcription factors. This review highlights contributions of E2A, hematopoietic transcription factor PU.1, growth factor independence (Gfi)-1, T cell factor (TCF)-1, and Runx factors and their interactions with the Notch pathway to promote T cell development.

E2A and Runx family factors have been implicated in establishing competent precursors in which Notch signaling can induce the T cell program. An early role was also indicated for PU.1. Later PU.1 activities are antagonistic to pro-T cell factors, however, including E proteins, Myb, Gfi-1, and TCF-1. Diversion to a non-T lineage can be promoted by PU.1, CCAAT/enhancer binding protein, or even GATA and TCF, but these diversion mechanisms are blocked by Notch signaling. An emergent gene network summarizes the cross-regulatory relationships among these factors.

Entry into the T-cell pathway is controlled by a dynamic balance among essential regulatory factors that depend on Notch signaling not only to trigger initiation of the T-cell program but also to maintain the lineage fidelity of their collective action.