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Immunity. 2018 Nov 20;49(5):971-986.e5. doi: 10.1016/j.immuni.2018.09.009. Epub 2018 Nov 6.

High-Dimensional Single-Cell Analysis Identifies Organ-Specific Signatures and Conserved NK Cell Subsets in Humans and Mice.

Author information

1
Aix Marseille Univ, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
2
Immunology, Marseille Immunopole, Hôpital de la Timone, Assistance Publique des Hôpitaux de Marseille, France.
3
Aix Marseille Univ, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France; Immunology, Marseille Immunopole, Hôpital de la Timone, Assistance Publique des Hôpitaux de Marseille, France; Internal Medicine, Hôpital de la Timone, Assistance Publique des Hôpitaux de Marseille, Marseille, France.
4
General Surgery and Liver Transplantation, Hôpital de la Timone, Assistance Publique des Hôpitaux de Marseille, Marseille, France.
5
Aix Marseille Univ, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France; Immunology, Marseille Immunopole, Hôpital de la Timone, Assistance Publique des Hôpitaux de Marseille, France.
6
Aix Marseille Univ, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France; Immunology, Marseille Immunopole, Hôpital de la Timone, Assistance Publique des Hôpitaux de Marseille, France; Innate Pharma Research Laboratories, Innate Pharma, Marseille, France. Electronic address: vivier@ciml.univ-mrs.fr.

Abstract

Natural killer (NK) cells are innate lymphoid cells (ILCs) involved in antimicrobial and antitumoral responses. Several NK cell subsets have been reported in humans and mice, but their heterogeneity across organs and species remains poorly characterized. We assessed the diversity of human and mouse NK cells by single-cell RNA sequencing on thousands of individual cells isolated from spleen and blood. Unbiased transcriptional clustering revealed two distinct signatures differentiating between splenic and blood NK cells. This analysis at single-cell resolution identified three subpopulations in mouse spleen and four in human spleen, and two subsets each in mouse and human blood. A comparison of transcriptomic profiles within and between species highlighted the similarity of the two major subsets, NK1 and NK2, across organs and species. This unbiased approach provides insight into the biology of NK cells and establishes a rationale for the translation of mouse studies to human physiology and disease.

KEYWORDS:

ILC; NK cells; innate immunity; scRNA-seq

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