High-Dimensional Single-Cell Analysis Identifies Organ-Specific Signatures and Conserved NK Cell Subsets in Humans and Mice
Open accessAbstract
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.
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There is high concordance between genes upregulated in 'digested' PBMCs and those upregulated in tissue-resident cells following tissue digestion in the Pasciuto et al. and Crinier et al. studies.
“We also found a high concordance between genes that were upregulated in ‘digested’ PBMCs and those that were observed as upregulated in tissue-resident cells following tissue digestion in the Pasciuto et al.42 and Crinier et al.46 studies (Supplementary Fig. 13f).”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as Crinier et al.46
The Results report genes expressed more strongly in splenic than blood NK cells, supporting the use of Crinier et al. as a source for a tissue-cell gene signature. But the STAR Methods say the spleen specimens were mechanically disrupted, not digested; the paper therefore does not support describing those genes as upregulated following tissue digestion. The high-concordance comparison is the citing authors’ own finding, not one attributed to Crinier et al. (LLM, conf=0.86)
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- Authors
- Crinier, A., Milpied, P., Escalière, B., Piperoglou, C., Galluso, J., Balsamo, A., Spinelli, L., Cervera-Marzal, I., Ebbo, M., Girard-Madoux, M., Jaeger, S., Bollon, E., Hamed, S., Hardwigsen, J., Ugolini, S., Vély, F., Narni-Mancinelli, E., & Vivier, E.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Assistance Publique Hôpitaux de Marseille (FR)
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 49
- Issue
- 5
- Pages
- 971-986.e5
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC6269138
- OpenAlex
- W2899566169
- Cited by
- 470
- References
- 3
- Citations by year
- 2026: 33 · 2025: 56 · 2024: 56 · 2023: 66 · 2022: 76 · 2021: 65 · 2020: 72 · 2019: 44 · 2018: 2
- FWCI
- 19.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Immunity (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- European Research Council (694502)
- Agence Nationale de la Recherche (ANR-15-CE15-0016-01)
- Ligue Nationale contre le Cancer (EL2017.LNCC/ErV)
- MSDAvenir (161204A50)
- Innate Pharma (10406A20/V)
- INSERM
- CNRS
- Aix-Marseille University
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- natural killer cells, NK cell subsets, splenic NK cells, innate lymphoid cells, cross-species comparison, NK cell heterogeneity
- MeSH terms
- Animals, Humans, Immunity, Innate, Killer Cells, Natural, Organ Specificity, Phenotype, Biomarkers, Immunophenotyping, Lymphocyte Subsets, Computational Biology, Gene Expression Profiling, Mice, Single-Cell Analysis, High-Throughput Nucleotide Sequencing, Transcriptome
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