Heterogeneity of human bone marrow and blood natural killer cells defined by single-cell transcriptome.

Autor: Yang C; Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA.; Departments of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA., Siebert JR; Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA.; Departments of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA., Burns R; Bioinfomatics Core, Blood Research Institute, Versiti, Milwaukee, WI, USA., Gerbec ZJ; Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA.; Departments of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA., Bonacci B; Flow Cytometry Core, Blood Research Institute, Versiti, Milwaukee, WI, USA., Rymaszewski A; Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA., Rau M; Departments of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA., Riese MJ; Departments of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA.; Laboratory of Lymphocyte Biology, Blood Research Institute, Versiti, Milwaukee, WI, USA.; Departments of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA., Rao S; Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.; Laboratory of Stem Cell Transcriptional Regulation, Blood Research Institute, Versiti, Milwaukee, WI, USA.; Departments of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA., Carlson KS; Departments of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.; Laboratory of Coagulation Biology, Blood Research Institute, Versiti, Milwaukee, WI, USA., Routes JM; Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA., Verbsky JW; Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA., Thakar MS; Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA.; Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA., Malarkannan S; Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA. subra.malar@bcw.edu.; Departments of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA. subra.malar@bcw.edu.; Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA. subra.malar@bcw.edu.; Departments of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. subra.malar@bcw.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Sep 02; Vol. 10 (1), pp. 3931. Date of Electronic Publication: 2019 Sep 02.
DOI: 10.1038/s41467-019-11947-7
Abstrakt: Natural killer (NK) cells are critical to both innate and adaptive immunity. However, the development and heterogeneity of human NK cells are yet to be fully defined. Using single-cell RNA-sequencing technology, here we identify distinct NK populations in human bone marrow and blood, including one population expressing higher levels of immediate early genes indicative of a homeostatic activation. Functionally matured NK cells with high expression of CX3CR1, HAVCR2 (TIM-3), and ZEB2 represents terminally differentiated status with the unique transcriptional profile. Transcriptomic and pseudotime analyses identify a transitional population between CD56 bright and CD56 dim NK cells. Finally, a donor with GATA2 T354M mutation exhibits reduced percentage of CD56 bright NK cells with altered transcriptome and elevated cell death. These data expand our understanding of the heterogeneity and development of human NK cells.
Databáze: MEDLINE