Immune Cell Function and Interaction
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Three prominent NK cell subsets in healthy human blood are identified: NK1, NK2 and NK3, further differentiated into six distinct subgroups, which suggest two separate ontogenetic origins for NK cells, leading to divergent transcriptional trajectories.
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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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@article{Moretta2024High,
title = {High-dimensional single-cell analysis of human natural killer cell heterogeneity},
author = {Lorenzo Moretta and Lucas Rebuffet and Janine Melsen and Bertrand Escalière and Daniela Basurto-Lozada and Avinash Bhandoola and Niklas K. Björkström and Yenan T. Bryceson and Roberta Castriconi and Frank Cichocki and Marco Colonna and Daniel M. Davis and Andreas Diefenbach and Yi Ding and Muzlifah Haniffa and Amir Horowitz and Lewis L. Lanier and Karl‐Johan Malmberg and Jeffrey S. Miller and Émilie Narni-Mancinelli and Luke O'neill and Chiara Romagnani and Dylan G. Ryan and Simona Sivori and Dan Sun and Constance Vagne and Éric Vivier},
journal = {Nature Immunology},
year = {2024},
doi = {10.1038/s41590-024-01883-0},
url = {https://doi.org/10.1038/s41590-024-01883-0}
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