T Cell Lineage Commitment: Identity and Renunciation

Precursors undertaking T cell development shed their access to other pathways in a sequential process that begins before entry into the thymus and continues through many cell cycles afterward. This process involves three levels of regulatory change, in which the cells' intrinsic transcriptional regulatory factors, expression of signaling receptors (e.g., Notch1), and expression of distinct homing receptors separately contribute to confirmation of T cell identity. Each alternative potential has a different underlying molecular basis that is neutralized and then permanently silenced through different mechanisms in early T cell precursors. This regulatory mosaic has notable implications for the hierarchy of relationships linking T lymphocytes to other hematopoietic fates.