Tcf1 regulates T lymphocyte lineage fidelity through its target genes Gata3 and Bcl11b

T cell factor 1 (Tcf1) is the first T cell?specific protein induced in multipotent progenitors following Notch signaling in the thymus, leading to the activation of two major target genes, Gata3 and Bcl11b. Tcf1 deficiency results in partial arrests in T cell development high apoptosis, and increased development of B cells and myeloid cells. Phenotypically, fully T cell?committed, Tcf1-deficient thymocytes have promiscuous gene expression, an altered epigenetic profile and can de-differentiate into more immature thymocytes and non-T cells. Expressing Bcl11b in Tcf1-deficient cells rescues T cell development, but does not strongly suppress the development of non-T cells; in contrast, expressing Gata3 suppresses the development of non-T cells, but does not rescue T cell development. Thus, T cell development is controlled by a minimal transcription factor network involving Notch signaling, Tcf1, and the subsequent division of labor between Bcl11b and Gata3, thereby ensuring a properly regulated T cell gene expression program Overall design: 15,000 sorted DN3a (Lin - CD25 + CD44 - CD27 - ) and DN3b (Lin - CD25 + CD44 - CD27 + )cells