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

Single-cell transcriptional profiling of human thymic stroma uncovers novel cellular heterogeneity in the thymic medulla.
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DOI:
10.1038/s41467-021-21346-6
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发表时间:
2021-02-17
影响因子:
16.6
通讯作者:
Parent AV
Parent AV
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bautista JL;Cramer NT;Miller CN;Chavez J;Berrios DI;Byrnes LE;Germino J;Ntranos V;Sneddon JB;Burt TD;Gardner JM;Ye CJ;Anderson MS;Parent AV

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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. The thymus supports T cell immunity by providing the environment for thymocyte differentiation. Here the authors profile human thymic stroma at the single cell level, identifying ionocytes as a new medullary population and defining tissue specific antigen expression in multiple stromal cell types.
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