In-depth functional and morphological characterization of the thymic vascular network 4136

Description The thymus is the primary lymphoid organ responsible for T cell development. Its importance for immune surveillance and tolerance, along with its regenerative capacity after stressor-induced involution, render the thymic microenvironment vital for understanding thymic functions and regeneration. Most studies have focused on the complexity of the, undoubtedly essential, Thymic Epithelial Cells (TEC). However, lack of insights on non-epithelial stromal cells is hindering the progress on how, during homeostasis and regeneration, these cells affect thymopoiesis. To address this, we combined single-cell ATAC-sequencing with subsequent confocal microscopy to establish topological features of the murine non-epithelial stroma. Chromatin accessibility patterns of both endothelial and mural cell (smooth muscle cells and pericytes) clusters, suggested a wide vessel heterogeneity. In-depth imaging of these intrathymic blood vessels further categorized them into arterial, capillary, venular, and lymphatic vessels, which were also strictly localized to unique cortical and medullary thymic compartments. Mural cells vastly differed in density, distribution, and morphology between different vessels. Our results also identified novel vascular features, including an auxiliary circulation in the subcapsular cortex and arteriovenous anastomoses within the corticomedullary junction and the cortical parenchyma. Our efforts illuminate for the first time the enriched vascular network of the thymus. Funding Sources Supported by the Albert Einstein College of Medicine Recruitment Fund, 3A3218 Topic Categories Hematopoiesis and Immune System Development (HEM)