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.
Authors
- Bryan R. Helm (ORCID: https://orcid.org/0000-0003-3386-7842)
- Lauren I. R. Ehrlich (ORCID: https://orcid.org/0000-0002-1697-1755)
- Ellen R. Richie (ORCID: https://orcid.org/0000-0003-0786-973X)
- Nancy R. Manley (ORCID: https://orcid.org/0000-0001-8489-7764)
- Andrew N. Macintyre (ORCID: https://orcid.org/0000-0002-5297-0207)
- Nandini Singarapu
- Scott Casey
- Erin Baker (ORCID: https://orcid.org/0000-0002-4139-9930)
- Aparna Calindi
- Ken S. Lau (ORCID: https://orcid.org/0000-0001-8438-0319)
- Anusha Vasudev (ORCID: https://orcid.org/0000-0001-8901-2451)
- Jayashree Srinivasan (ORCID: https://orcid.org/0000-0001-9478-7518)
- Seungwoo Kang (ORCID: https://orcid.org/0000-0003-1301-8480)
- Laura P. Hale (ORCID: https://orcid.org/0000-0001-5707-0390)
- Qi Liu (ORCID: https://orcid.org/0000-0001-8892-7078)
- Colin E. Moore (ORCID: https://orcid.org/0000-0001-7277-7343)
- Siddhartha Shah
- Ruiting Zong
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- University of California, Los Angeles (US)
- University of Georgia (US)
- Duke University (US)
- Vanderbilt University (US)
- The University of Texas at Austin (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.116677
- Citations
- 1
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- University of Texas at Austin
- National Institutes of Health
- University of Texas MD Anderson Cancer Center
- National Institute of Allergy and Infectious Diseases