A cell atlas of human thymic development defines T cell repertoire formation
Rachel A Botting,
Cecilia Dominguez Conde,
Daniel J Kunz,
John Robert Ferdinand,
Steven N Lisgo,
Kerstin B Meyer,
Menna R Clatworthy,
Sarah A. Teichmann
Posted 28 Jan 2020
bioRxiv DOI: 10.1101/2020.01.28.911115 (published DOI: 10.1126/science.aay3224)
Posted 28 Jan 2020
The thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We utilised single-cell RNA-sequencing (scRNA-seq) to create a cell census of the human thymus and to reconstruct T-cell differentiation trajectories and T-cell receptor (TCR) recombination kinetics. Using this approach, we identified and located in situ novel CD8aa+ T-cell populations, thymic fibroblast subtypes and activated dendritic cell (aDC) states. In addition, we reveal a bias in TCR recombination and selection, which is attributed to genomic position and suggests later commitment of the CD8+ T-cell lineage. Taken together, our data provide a comprehensive atlas of the human thymus across the lifespan with new insights into human T-cell development.
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