T Cell Development: Old Tales Retold By Single-Cell RNA Sequencing

Mammalian T cell development initiates from the migration of hematopoietic progenitors to the thymus, which undergo cell proliferation, T-lineage specification and commitment, as well as positive and negative selection. These processes are precisely controlled at multiple levels and have been intensively studied using gene-modified animal models and in vitro coculture systems. However, several long-standing questions, including the characterization of the rare but crucial progenitors/precursors and the molecular mechanisms underlying their fate decision, have been dampened because of cell scarcity and lack of appropriate techniques. Single-cell RNA sequencing (scRNA-seq) makes it possible to investigate and resolve some of these questions, leading to new remarkable progress in identifying and characterizing early thymic progenitors and delineating the refined developmental trajectories of conventional and unconventional T cells. Single-cell technology is a powerful tool to dissect the heterogeneity and characteristics of rare cell populations during mammalian T cell development.T cell development in human fetal and postnatal development has been studied at the transcriptional level and at single-cell resolution.New insights regarding thymus seeding progenitors and early thymic progenitors have been unveiled using single-cell sequencing.The development of unconventional T cells and innate lymphoid cells continues to be deciphered and is aided by single-cell sequencing.