Coordinated Changes in Stromal and Hematopoietic Cells That Define the Perinatal to Juvenile Transition in the Mouse Thymus

Authors

Anusha Vasudev
Colin R Moore
Aparna Calindi
Seung Woo Kang
Bryan R Helm
Jayashree Srinivasan
Siddhartha Shah
Erin Baker
Ruiting Zong
Nandini Singarapu
Scott Casey
Andrew N Macintyre
Ken S Lau
Laura P Hale
Qi Liu
Nancy R Manley
Lauren I R Ehrlich
Ellen R Richie

Language

English

Publication Date

12-23-2025

Journal

Cell Reports

DOI

10.1016/j.celrep.2025.116677

PMID

41389204

Abstract

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.

Keywords

Animals, Thymus Gland, Stromal Cells, Mice, Mice, Inbred C57BL, Hematopoietic Stem Cells, Cell Differentiation, Female, Thymocytes, Epithelial Cells, CP: Developmental biology, CP: Immunology, E2F, IGF2, interferon I/III, neonatal thymus, perinatal thymocytes, retinoblastoma protein, thymic dendritic cells, thymic epithelial cells, thymic mesenchyme, thymus atlas

Published Open-Access

yes

Recommended Citation

Vasudev, Anusha; Moore, Colin R; Calindi, Aparna; et al., "Coordinated Changes in Stromal and Hematopoietic Cells That Define the Perinatal to Juvenile Transition in the Mouse Thymus" (2025). Faculty, Staff and Student Publications. 6462.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6462