의생명시스템학부

제목: A single cell atlas of human thymus across development and aging defines dynamics of T cell development

내용:

The thymus is the critical organ for T-cell development and T-cell receptor (TCR) repertoire formation, which shapes the landscape of adaptive immunity. While the thymus has been extensively studied using diverse animal models, the detailed atlas of human thymus is required to understand human immunity. To provide a comprehensive atlas of thymic cells across human life, we performed scRNAseq using dissociated cells from human thymus during development, childhood and adult life. We identified more than 50 different cell states in the human thymus, which dynamically change in abundance and gene expression profiles across development, paediatric and adult life. We computationally predicted the trajectory of human T-cell development from early progenitors in the hematopoietic fetal liver into diverse mature T cell types. Using this trajectory, we constructed a framework of putative transcription factors driving T-cell fate determination. Among thymic unconventional T cells, we noted a distinct subset of CD8ɑɑ+T cells, which is marked by GNG4 expression and uniquely located in the peri-medullary region of the thymus. This subset expressed high levels of XCL1 and co-localised with XCR1+ dendritic cells (DC1). Finally, we identified a strong bias in human VDJ usage shaped by recombination and multiple rounds of selection, including a TCRɑ V-J bias for CD8+ T cells. Our single-cell transcriptome profile of the thymus across human lifetime and across species provides a high-resolution census of T-cell development within the native tissue microenvironment. Systematic comparison between human and mouse thymus highlights human-specific cell states and gene expression signatures. Our detailed cellular network of the thymic niche for T-cell development will aid the establishment of in vitro organoid culture models that faithfully recapitulate human in vivo thymic tissue.