Coordinated changes in stromal and hematopoietic cells that define the perinatal to juvenile transition in the mouse thymus

Perinatal T cells have distinctive phenotypes and functions that may be due in part to age-associated features of stromal cells in the perinatal thymus. We identify age-associated changes in mouse thymic epithelial cells, mesenchyme, endothelium, and hematopoietic antigen-presenting cells from birth to one month of age using single-cell transcriptional profiling, flow cytometry, and imaging. Coordinated cellular and molecular changes occur at 7–14 days of age, designated “transitional ages,” as thymus growth switches to homeostasis. E2F target gene expression declines, and the expression of type I interferon response genes increases across diverse cell types at transitional ages. Alterations in thymic stromal cells coincide with elevated markers of thymocyte self-reactivity and enhanced Treg suppressive phenotypes and function. The integrated results reveal coordinated remodeling of multiple stromal cell types during the perinatal to juvenile transition, which likely impacts T cell differentiation. These datasets provide a resource for the investigation of the perinatal thymus environment.