Journal
SCIENCE
Volume 367, Issue 6480, Pages 868-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aay3224
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Funding
- Wellcome Human Cell Atlas Strategic Science Support [WT211276/Z/18/Z]
- Chan Zuckerberg Initiative [CZF2019-002445]
- Wellcome [WT107931/Z/15/Z, WT206194]
- ERC Consolidator [646794]
- EU MRG-Grammar awards
- Lister Institute for Preventive Medicine
- NIHR
- Research Foundation Flanders (FWO) [G053816N]
- Ghent University Special Research Fund [BOF18-GOA-024]
- EMBO Long-Term Fellowship
- Wellcome Trust [203828/Z/16/A, 203828/Z/16/Z]
- European Research Council [ERC-Stg 639429]
- Rosetrees Trust [M362, M362-F1]
- UCL Therapeutic Acceleration Support Fund
- GOSH BRC
- NIHR funding
- WT MRC Cambridge Stem Cell Institute
- Newcastle-Biomedical Research Centre
- Wellcome Trust [203828/Z/16/A, 203828/Z/16/Z] Funding Source: Wellcome Trust
- MRC [MC_PC_17180, MC_PC_17230, MR/R006237/1, MR/S035842/1] Funding Source: UKRI
- European Research Council (ERC) [646794] Funding Source: European Research Council (ERC)
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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 used single-cell RNA sequencing to create a cell census of the human thymus across the life span and to reconstruct T cell differentiation trajectories and T cell receptor (TCR) recombination kinetics. Using this approach, we identified and located in situ CD8 alpha alpha(+) T cell populations, thymic fibroblast subtypes, and activated dendritic cell states. In addition, we reveal a bias in TCR recombination and selection, which is attributed to genomic position and the kinetics of lineage commitment. Taken together, our data provide a comprehensive atlas of the human thymus across the life span with new insights into human T cell development.
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