Multi-tissue single-cell analysis deconstructs the complex programs of mouse natural killer and type 1 innate lymphoid cells in tissues and circulation

Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s) are heterogenous innate lymphocytes broadly defined in mice as Lin(-) NK1.1(+)NKp46(+) cells that express the transcription factor T-BET and produce interferon-gamma. The ILC1 definition primarily stems from studies on liver and small intestinal populations. However, NK1.1(+)NKp46(+) cells in the salivary glands, uterus, adipose, and other tissues exhibit nonuniform programs that differ from those of liver or intestinal ILC1s or NK cells. Here, we performed single-cell RNA sequencing on murine NK1.1(+)NKp46(+) cells from blood, spleen, various tissues, and solid tumors. We identified gene expression programs of tissue-specific ILC1s, tissue-specific NK cells, and non-tissue-specific populations in blood, spleen, and other tissues largely corresponding to circulating cells. Moreover, we found that circulating NK cell programs were reshaped in tumor-bearing mice. Core programs of circulating and tumor NK cells paralleled conserved human NK cells signatures, advancing our understanding of the human NK-ILC1 spectrum.

Automated summary

NK cells and ILC1s are heterogenous innate lymphocytes characterized by specific gene expression programs in different tissues, including blood, spleen, and solid tumors. The programs of circulating NK cells were found to be reshaped in tumor-bearing mice, with conserved signatures similar to human NK cells. This study advances the understanding of the NK-ILC1 spectrum in both murine and human systems.