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Single-cell analysis of human fetal and post-natal γδ thymocytes reveals distinct functional programming.

ABSTRACT: Developmental thymic waves of innate-like and adaptive-like gd T cells have been described, but the current understanding of γδ T cell development is mainly limited to mouse models. Here, we combined single cell (sc) RNA gene expression and sc γδ T cell receptor (TCR) sequencing on fetal and pediatric γδ thymocytes in order to understand the ontogeny of human γδ T cells. Mature fetal γδ thymocytes were committed to either a type 1, a type 3 or type 2-like effector fate, independent from γδ T cell subset type (Vγ9Vδ2 vs nonVγ9Vδ2), and were enriched for public CDR3 features upon maturation. Strikingly, type 1, type 3 and type 2 cells expressed different CDR3 sequences and followed distinct developmental trajectories. In contrast, the pediatric thymus generated only a small effector subset that was highly biased towards Vγ9Vδ2 TCR usage and showed a mixed type 1/type 3 effector profile. Thus, our combined dataset of gene expression and detailed TCR information at the single-cell level defines γδ thymocyte development in human and provides a resource for further study.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180059 | GEO | 2022/08/19

REPOSITORIES: GEO

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