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Single-cell transcriptional profiling of human thymic stroma uncovers novel cellular heterogeneity in the thymic medulla

Author

Listed:
  • Jhoanne L. Bautista

    (University of California, San Francisco
    University of California, San Francisco)

  • Nathan T. Cramer

    (University of California, San Francisco)

  • Corey N. Miller

    (University of California, San Francisco)

  • Jessica Chavez

    (University of California, San Francisco)

  • David I. Berrios

    (University of California, San Francisco)

  • Lauren E. Byrnes

    (University of California, San Francisco)

  • Joe Germino

    (University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco)

  • Vasilis Ntranos

    (University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco)

  • Julie B. Sneddon

    (University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco)

  • Trevor D. Burt

    (University of California, San Francisco
    University of California, San Francisco
    Duke University School of Medicine)

  • James M. Gardner

    (University of California, San Francisco
    University of California, San Francisco)

  • Chun J. Ye

    (University of California, San Francisco
    San Francisco
    University of California, San Francisco
    Chan Zuckerberg Biohub)

  • Mark S. Anderson

    (University of California, San Francisco)

  • Audrey V. Parent

    (University of California, San Francisco)

Abstract

The thymus’ key function in the immune system is to provide the necessary environment for the development of diverse and self-tolerant T lymphocytes. While recent evidence suggests that the thymic stroma is comprised of more functionally distinct subpopulations than previously appreciated, the extent of this cellular heterogeneity in the human thymus is not well understood. Here we use single-cell RNA sequencing to comprehensively profile the human thymic stroma across multiple stages of life. Mesenchyme, pericytes and endothelial cells are identified as potential key regulators of thymic epithelial cell differentiation and thymocyte migration. In-depth analyses of epithelial cells reveal the presence of ionocytes as a medullary population, while the expression of tissue-specific antigens is mapped to different subsets of epithelial cells. This work thus provides important insight on how the diversity of thymic cells is established, and how this heterogeneity contributes to the induction of immune tolerance in humans.

Suggested Citation

  • Jhoanne L. Bautista & Nathan T. Cramer & Corey N. Miller & Jessica Chavez & David I. Berrios & Lauren E. Byrnes & Joe Germino & Vasilis Ntranos & Julie B. Sneddon & Trevor D. Burt & James M. Gardner &, 2021. "Single-cell transcriptional profiling of human thymic stroma uncovers novel cellular heterogeneity in the thymic medulla," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21346-6
    DOI: 10.1038/s41467-021-21346-6
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    Cited by:

    1. Yanchuan Li & Huamei Li & Cheng Peng & Ge Meng & Yijun Lu & Honglin Liu & Li Cui & Huan Zhou & Zhu Xu & Lingyun Sun & Lihong Liu & Qing Xiong & Beicheng Sun & Shiping Jiao, 2024. "Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling," Nature Communications, Nature, vol. 15(1), pages 1-25, December.

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