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

Author

Listed:
  • Chao Yang

    (Blood Research Institute, Versiti
    Medical College of Wisconsin)

  • Jason R. Siebert

    (Blood Research Institute, Versiti
    Medical College of Wisconsin)

  • Robert Burns

    (Blood Research Institute, Versiti)

  • Zachary J. Gerbec

    (Blood Research Institute, Versiti
    Medical College of Wisconsin)

  • Benedetta Bonacci

    (Blood Research Institute, Versiti)

  • Amy Rymaszewski

    (Medical College of Wisconsin)

  • Mary Rau

    (Medical College of Wisconsin)

  • Matthew J. Riese

    (Medical College of Wisconsin
    Blood Research Institute, Versiti
    Medical College of Wisconsin)

  • Sridhar Rao

    (Medical College of Wisconsin
    Blood Research Institute, Versiti
    Medical College of Wisconsin)

  • Karen-Sue Carlson

    (Medical College of Wisconsin
    Blood Research Institute, Versiti)

  • John M. Routes

    (Medical College of Wisconsin)

  • James W. Verbsky

    (Medical College of Wisconsin)

  • Monica S. Thakar

    (Blood Research Institute, Versiti
    Medical College of Wisconsin)

  • Subramaniam Malarkannan

    (Blood Research Institute, Versiti
    Medical College of Wisconsin
    Medical College of Wisconsin
    Medical College of Wisconsin)

Abstract

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 CD56bright and CD56dim NK cells. Finally, a donor with GATA2T354M mutation exhibits reduced percentage of CD56bright NK cells with altered transcriptome and elevated cell death. These data expand our understanding of the heterogeneity and development of human NK cells.

Suggested Citation

  • Chao Yang & Jason R. Siebert & Robert Burns & Zachary J. Gerbec & Benedetta Bonacci & Amy Rymaszewski & Mary Rau & Matthew J. Riese & Sridhar Rao & Karen-Sue Carlson & John M. Routes & James W. Verbsk, 2019. "Heterogeneity of human bone marrow and blood natural killer cells defined by single-cell transcriptome," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11947-7
    DOI: 10.1038/s41467-019-11947-7
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    Cited by:

    1. Adele M. Alchahin & Shenglin Mei & Ioanna Tsea & Taghreed Hirz & Youmna Kfoury & Douglas Dahl & Chin-Lee Wu & Alexander O. Subtelny & Shulin Wu & David T. Scadden & John H. Shin & Philip J. Saylor & D, 2022. "A transcriptional metastatic signature predicts survival in clear cell renal cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Pulak R. Nath & Mary Maclean & Vijay Nagarajan & Jung Wha Lee & Mehmet Yakin & Aman Kumar & Hadi Nadali & Brian Schmidt & Koray D. Kaya & Shilpa Kodati & Alice Young & Rachel R. Caspi & Jonas J. W. Ku, 2024. "Single-cell profiling identifies a CD8bright CD244bright Natural Killer cell subset that reflects disease activity in HLA-A29-positive birdshot chorioretinopathy," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Nicholas L. Dooley & Tinashe G. Chabikwa & Zuleima Pava & Jessica R. Loughland & Julianne Hamelink & Kiana Berry & Dean Andrew & Megan S. F. Soon & Arya SheelaNair & Kim A. Piera & Timothy William & B, 2023. "Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    4. Ziqi Zhang & Haoran Sun & Ragunathan Mariappan & Xi Chen & Xinyu Chen & Mika S. Jain & Mirjana Efremova & Sarah A. Teichmann & Vaibhav Rajan & Xiuwei Zhang, 2023. "scMoMaT jointly performs single cell mosaic integration and multi-modal bio-marker detection," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Taghreed Hirz & Shenglin Mei & Hirak Sarkar & Youmna Kfoury & Shulin Wu & Bronte M. Verhoeven & Alexander O. Subtelny & Dimitar V. Zlatev & Matthew W. Wszolek & Keyan Salari & Evan Murray & Fei Chen &, 2023. "Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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