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Blood advances
04 14, 2020;4 (7): 1388-1406.

Diversity of peripheral blood human NK cells identified by single-cell RNA sequencing.

Samantha L Smith, Philippa R Kennedy, Kevin B Stacey, Jonathan D Worboys, Annie Yarwood, Seungmae Seo, Everardo Hegewisch Solloa, Brandon Mistretta, Sujash S Chatterjee, Preethi Gunaratne, Kimaada Allette, Ying-Chih Wang, Melissa Laird Smith, Robert Sebra, Emily M Mace, Amir Horowitz, Wendy Thomson, Paul Martin, Steve Eyre, Daniel M Davis
Author Information
  1. Samantha L Smith: The Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, and.
  2. Philippa R Kennedy: The Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, and.
  3. Kevin B Stacey: The Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, and.
  4. Jonathan D Worboys: The Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, and.
  5. Annie Yarwood: Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom.
  6. Seungmae Seo: Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY.
  7. Everardo Hegewisch Solloa: Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY.
  8. Brandon Mistretta: Department of Biochemistry, University of Houston, Houston, TX; and.
  9. Sujash S Chatterjee: Department of Biochemistry, University of Houston, Houston, TX; and.
  10. Preethi Gunaratne: Department of Biochemistry, University of Houston, Houston, TX; and.
  11. Kimaada Allette: Department of Genetics and Genomic Sciences, and.
  12. Ying-Chih Wang: Department of Genetics and Genomic Sciences, and.
  13. Melissa Laird Smith: Department of Genetics and Genomic Sciences, and.
  14. Robert Sebra: Department of Genetics and Genomic Sciences, and.
  15. Emily M Mace: Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY.
  16. Amir Horowitz: Department of Oncological Sciences, Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
  17. Wendy Thomson: Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom.
  18. Paul Martin: The Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, and.
  19. Steve Eyre: Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom.
  20. Daniel M Davis: The Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, and.
PMID: 32271902 DOI: 10.1182/bloodadvances.2019000699

Abstract

Human natural killer (NK) cells in peripheral blood perform many functions, and classification of specific subsets has been a longstanding goal. We report single-cell RNA sequencing of NK cells, comparing gene expression in unstimulated and interleukin (IL)-2-activated cells from healthy cytomegalovirus (CMV)-negative donors. Three NK cell subsets resembled well-described populations; CD56brightCD16-, CD56dimCD16+CD57-, and CD56dimCD16+CD57+. CD56dimCD16+CD57- cells subdivided to include a population with higher chemokine mRNA and increased frequency of killer-cell immunoglobulin-like receptor expression. Three novel human blood NK cell populations were identified: a population of type I interferon-responding NK cells that were CD56neg; a population exhibiting a cytokine-induced memory-like phenotype, including increased granzyme B mRNA in response to IL-2; and finally, a small population, with low ribosomal expression, downregulation of oxidative phosphorylation, and high levels of immediate early response genes indicative of cellular activation. Analysis of CMV+ donors established that CMV altered the proportion of NK cells in each subset, especially an increase in adaptive NK cells, as well as gene regulation within each subset. Together, these data establish an unexpected diversity in blood NK cells and provide a new framework for analyzing NK cell responses in health and disease.

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Grants

  1. 110091/Wellcome Trust
  2. MC_PC_15072/Medical Research Council
  3. 20385/Versus Arthritis
  4. 21745/Versus Arthritis
  5. R21 AI130760/NIAID NIH HHS
  6. /Wellcome Trust
  7. 202865/Z/16/Z/Wellcome Trust

MeSH Term

Cytomegalovirus
Cytomegalovirus Infections
Humans
Killer Cells, Natural
Receptors, KIR
Sequence Analysis, RNA

Chemicals

Receptors, KIR
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Links to CNCB-NGDC Resources

GEN: GEND000132 (Diversity of peripheral blood human NK cells identified by single cell RNA sequencing)

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