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.

Carbon nanodots (CNDs) have shown potential for antioxidative activity at the cellular level.Here we applied a facile hydrothermal method to prepare fluorescent nitrogen and sulfur (N,S-) codoped CNDs using α-lipoic acid, citric acid, and urea as precursor molecules. This work describes a comprehensive study for exploring their antioxidation activity using UV-vis absorption and electrochemistry measurements of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH • ), as well as a lucigenin chemiluminescence (lucigenin-CL) assay. The lucigenin-CL assay detects superoxide anion radicals, i.e., reactive oxygen species (ROS) produced through the xanthine/xanthine oxidase (XO) reaction. The electrochemically derived relationship between the unreacted nitrogen-centered DPPH • and CND concentrations agrees with that obtained from UV-vis measurements. A reaction pathway for the ROS antioxidative reaction of N,S-codoped CNDs is proposed. These findings should aid in the development of N,S-codoped CNDs for practical use in biomedical applications.

Highlights d Deletion of individual HLA genes protects b cells from T-cellmediated rejection d Genome editing of stem cells does not affect their b cell differentiation potential d Retention of HLA-A2 promotes surface expression of HLA-E and reduces NK cell activity d HLA-A2 retention reduces rejection while allowing immune surveillance of the graft

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