The power of single-cell genomics stems from the ability to explore cell types and cell states in an unbiased way, which can lead to surprising new insights relating to developmental changes, tissue architecture and disease mechanisms. 2019 has yielded an exceptional number of high-quality, single-cell studies of the immune system in development, homeostasis and disease. Here, we highlight a selection of these.
Key advances
The combination of single-cell RNA sequencing (scRNA-seq) with flow cytometry and imaging mass cytometry has provided a new perspective on the haematopoietic functions of the human embryonic and fetal liver.
Mass cytometry and scRNA-seq have been used to dissect the CD4+ T cell landscape in the human intestinal lamina propria during pregnancy, showing that the human fetal gut contains memory-like CD4+ T cells.
Exploring the transcriptomic landscape of regulatory T (Treg) cells across lymphoid and non-lymphoid tissues has shown the gene expression programmes that are involved in the tissue adaptation trajectories of Treg cells.
The identification of increased numbers of lipid-associated macrophages in obesity shows how single-cell technologies can be used to investigate disease pathogenesis.
In patients with ulcerative colitis, scRNA-seq has uncovered the rewiring of immune cell networks involved in disease and therapy resistance.
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References
Gomes, T., Teichmann, S. A. & Talavera-López, C. Immunology driven by large-scale single-cell sequencing. Trends Immunol. 40, 1011–1021 (2019).
Popescu, D. et al. Decoding human fetal liver haematopoiesis. Nature 574, 365–371 (2019).
Schneider, C. et al. Tissue-resident group 2 innate lymphoid cells differentiate by layered ontogeny and in situ perinatal priming. Immunity 50, 1425–1438.e5 (2019).
Li, N. et al. Memory CD4+ T cells are generated in the human fetal intestine. Nat. Immunol. 20, 301–312 (2019).
Miragaia, R. J. et al. Single-cell transcriptomics of regulatory T cells reveals trajectories of tissue adaptation. Immunity 50, 493–504.e7 (2019).
Jaitin, D. A. et al. Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner. Cell 178, 686–698.e14 (2019).
Hill, D. A. et al. Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue. Proc. Natl Acad. Sci. USA 115, E5096–E5105 (2018).
Smillie, C. S. et al. Intra- and inter-cellular rewiring of the human colon during ulcerative colitis. Cell 178, 714–730.e22 (2019).
West, N. R. et al. Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease. Nat. Med. 23, 579–589 (2017).
Acknowledgements
The authors thank M. Haniffa, T. Gomes and W. Sungnak for the critical reading of the manuscript and J. Eliasova for the illustration work.
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S.A.T. has received consulting fees from Genentech, Biogen and Roche. C.D.C. declares no competing interests.
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Human Cell Atlas: https://www.humancellatlas.org/
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Domínguez Conde, C., Teichmann, S.A. Deciphering immunity at high plexity and resolution. Nat Rev Immunol 20, 77–78 (2020). https://doi.org/10.1038/s41577-019-0254-0
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DOI: https://doi.org/10.1038/s41577-019-0254-0
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