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Nat Immunol. 2016 Apr;17(4):451-60. doi: 10.1038/ni.3368. Epub 2016 Feb 15.

The heterogeneity of human CD127(+) innate lymphoid cells revealed by single-cell RNA sequencing.

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Ludwig Institute for Cancer Research, Stockholm, Sweden.
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Sweden.
Department of Oto-Rhino-Laryngology, Karolinska University Hospital and CLINTEC, Karolinska Institutet, Stockholm, Sweden.


Innate lymphoid cells (ILCs) are increasingly appreciated as important participants in homeostasis and inflammation. Substantial plasticity and heterogeneity among ILC populations have been reported. Here we have delineated the heterogeneity of human ILCs through single-cell RNA sequencing of several hundreds of individual tonsil CD127(+) ILCs and natural killer (NK) cells. Unbiased transcriptional clustering revealed four distinct populations, corresponding to ILC1 cells, ILC2 cells, ILC3 cells and NK cells, with their respective transcriptomes recapitulating known as well as unknown transcriptional profiles. The single-cell resolution additionally divulged three transcriptionally and functionally diverse subpopulations of ILC3 cells. Our systematic comparison of single-cell transcriptional variation within and between ILC populations provides new insight into ILC biology during homeostasis, with additional implications for dysregulation of the immune system.

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