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.