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Published on: February 22, 2020
Single cell atlas of canine natural killer cells identifies distinct circulating and tissue resident gene profiles
Aryana M Razmara1, Marshall Lammers1, Sean J Judge1
1Division of Surgical Oncology, Department of Surgery, University of California Davis School of Medicine, Sacramento, CA, United States.
Introduction:
Natural killer (NK) cells in mice and humans are key effectors of the innate immune system with complex immunoregulatory functions, and diverse subsets have been identified with distinct characteristics and roles. Companion dogs with spontaneous cancer have been validated as models of human disease, including cancer immunology and immunotherapy, and greater understanding of NK cell heterogeneity in dogs can inform NK biology across species and optimize NK immunotherapy for both dogs and people.
Methods:
Here, we assessed canine NK cell populations by single-cell RNA sequencing (scRNAseq) across blood, lung, liver, spleen, and placenta with comparison to human NK cells from blood and the same tissues to better characterize the differential gene expression of canine and human NK cells regarding ontogeny, heterogeneity, patterns of activation, inhibition, and tissue residence.
Results:
Overall, we observed tissue-specific NK cell signatures consistent with immature NK cells in the placenta, mature and activated NK cells in the lung, and NK cells with a mixed activated and inhibited signature in the liver with significant cross-species homology.
Discussion:
Together, our results point to heterogeneous canine NK populations highly comparable to human NK cells, and we provide a comprehensive atlas of canine NK cells across organs which will inform future cross-species NK studies and further substantiate the spontaneous canine model to optimize NK immunotherapy across species.
Insights
Canine natural killer (NK) cells show diverse, tissue-specific signatures comparable to human NK cells. This cross-species comparison advances understanding of NK cell biology and immunotherapy applications in both dogs and humans.
Area of Science:
- Immunology
- Comparative genomics
Background:
- Natural killer (NK) cells are crucial innate immune effectors with diverse roles.
- Companion dogs with cancer serve as valuable models for human disease research, including cancer immunology.
Purpose of the Study:
- To characterize canine NK cell heterogeneity across various tissues.
- To compare canine NK cell gene expression with human NK cells.
- To inform cross-species NK cell biology and immunotherapy.
Main Methods:
- Single-cell RNA sequencing (scRNAseq) of canine NK cells from blood, lung, liver, spleen, and placenta.
- Comparison of canine NK cell data with human NK cell data from corresponding tissues.
Main Results:
- Identified tissue-specific NK cell signatures in dogs, including immature cells in the placenta, activated cells in the lung, and mixed signatures in the liver.
- Observed significant cross-species homology in NK cell gene expression and function between dogs and humans.
Conclusions:
- Canine NK cell populations are highly heterogeneous and comparable to human NK cells.
- A comprehensive atlas of canine NK cells across organs was generated.
- Findings support the use of spontaneous canine cancer models for advancing NK cell research and immunotherapy across species.
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