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

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, Chun J. Ye, Mark S. Anderson and Audrey V. Parent ()
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Jhoanne L. Bautista: 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
Vasilis Ntranos: University of California, San Francisco
Julie B. Sneddon: University of California, San Francisco
Trevor D. Burt: University of California, San Francisco
James M. Gardner: University of California, San Francisco
Chun J. Ye: University of California, San Francisco
Mark S. Anderson: University of California, San Francisco
Audrey V. Parent: University of California, San Francisco

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21346-6

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