The effectors that induce T lineage specification and commitment downstream of Notch1 signals remain unknown. In Nature, Bhandoola and colleagues show that the transcription factor TCF-1 is a critical regulator of T cell specification. TCF-1 is induced in early T cell progenitors by Notch1 signaling and positively regulates its own expression. TCF-1-deficient progenitors inhibit alternative myeloid and B cell fates normally but fail to upregulate T cell–specific genes. Ectopic expression of TCF-1 in progenitor cells is sufficient to induce T cell development on OP9 stromal cells in the absence of Notch ligands or in Notch1-deficient progenitors in vivo. TCF-1 directly regulates the expression of many T cell–specific genes, including Gata3, Bcl11b, Cd3e and Il2ra, but not of established Notch1 targets such as Deltex1 and Ptcra. Appropriately, TCF-1 is an abbreviation of 'T cell factor 1'.

Nature 476, 63–68 (2011)