TY - JOUR
T1 - High-dimensional single-cell analysis of human natural killer cell heterogeneity
AU - Rebuffet, Lucas
AU - Melsen, Janine E.
AU - Escalière, Bertrand
AU - Basurto-Lozada, Daniela
AU - Bhandoola, Avinash
AU - Björkström, Niklas K.
AU - Bryceson, Yenan T.
AU - Castriconi, Roberta
AU - Cichocki, Frank
AU - Colonna, Marco
AU - Davis, Daniel M.
AU - Diefenbach, Andreas
AU - Ding, Yi
AU - Haniffa, Muzlifah
AU - Horowitz, Amir
AU - Lanier, Lewis L.
AU - Malmberg, Karl Johan
AU - Miller, Jeffrey S.
AU - Moretta, Lorenzo
AU - Narni-Mancinelli, Emilie
AU - O’Neill, Luke A.J.
AU - Romagnani, Chiara
AU - Ryan, Dylan G.
AU - Sivori, Simona
AU - Sun, Dan
AU - Vagne, Constance
AU - Vivier, Eric
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/8
Y1 - 2024/8
N2 - Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells. We identified three prominent NK cell subsets in healthy human blood: NK1, NK2 and NK3, further differentiated into six distinct subgroups. Our findings delineate the molecular characteristics, key transcription factors, biological functions, metabolic traits and cytokine responses of each subgroup. These data also suggest two separate ontogenetic origins for NK cells, leading to divergent transcriptional trajectories. Furthermore, we analyzed the distribution of NK cell subsets in the lung, tonsils and intraepithelial lymphocytes isolated from healthy individuals and in 22 tumor types. This standardized terminology aims at fostering clarity and consistency in future research, thereby improving cross-study comparisons.
AB - Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells. We identified three prominent NK cell subsets in healthy human blood: NK1, NK2 and NK3, further differentiated into six distinct subgroups. Our findings delineate the molecular characteristics, key transcription factors, biological functions, metabolic traits and cytokine responses of each subgroup. These data also suggest two separate ontogenetic origins for NK cells, leading to divergent transcriptional trajectories. Furthermore, we analyzed the distribution of NK cell subsets in the lung, tonsils and intraepithelial lymphocytes isolated from healthy individuals and in 22 tumor types. This standardized terminology aims at fostering clarity and consistency in future research, thereby improving cross-study comparisons.
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U2 - 10.1038/s41590-024-01883-0
DO - 10.1038/s41590-024-01883-0
M3 - Article
C2 - 38956378
AN - SCOPUS:85197467174
SN - 1529-2908
VL - 25
SP - 1474
EP - 1488
JO - Nature immunology
JF - Nature immunology
IS - 8
ER -