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

Adelle P. McFarland, Adam Yalin, Shuang Yin Wang, Victor S. Cortez, Tomer Landsberger, Raki Sudan, Vincent Peng, Hannah L. Miller, Biancamaria Ricci, Eyal David, Roberta Faccio, Ido Amit, Marco Colonna

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s) are heterogenous innate lymphocytes broadly defined in mice as LinNK1.1+NKp46+ cells that express the transcription factor T-BET and produce interferon-γ. 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.

Original languageEnglish
Pages (from-to)1320-1337.e4
JournalImmunity
Volume54
Issue number6
DOIs
StatePublished - Jun 8 2021

Keywords

  • EOMES
  • HOBIT
  • TCF-1
  • glycolysis
  • innate lymphoid cells
  • natural killer cells
  • single-cell RNA sequencing
  • tissue
  • transcription factor
  • tumor

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