Medullary epithelium-free areas in the rat thymus are specialized niches enriched for mature thymocytes and distinct stromal subsets
- 1Department of Anatomy, Dokkyo Medical University
- 2Laboratory for Molecular Pathobiology, Research Center for Advanced Medical Science, Dokkyo Medical University
Abstract
The thymic medulla provides the microenvironment for negative selection, late thymocyte maturation, and thymocyte egress, and is generally characterized by widespread distribution of medullary thymic epithelial cells (mTECs). In contrast, the rat thymic medulla contains medullary epithelium-free areas (mEFAs), but the cellular composition and functional significance of these regions remain unclear. Here, to address these questions, we combined spatial transcriptomic data with thymocyte and stromal scRNA-seq reference datasets using robust cell-type decomposition (RCTD) to characterize mEFAs. These analyses revealed that more mature phenotypes within the CD4SP, CD8SP, and regulatory T-cell lineages were preferentially localized in mEFAs, whereas immature SP subsets were enriched in medullary epithelium-containing areas. The newly identified rat thymic mesenchymal cell subsets TMC3 and TMC4 were also enriched in mEFAs. These subsets were broadly similar to mouse medullary fibroblasts but displayed distinct predicted interactions with SP thymocytes, including costimulatory molecule–receptor, chemokine–receptor, and ECM–integrin axes. In addition, venous endothelial cells (vECs) expressing portal endothelial cell markers were enriched in mEFAs. Spns2 , which encodes a transporter that releases S1P from cells into the extracellular space, was preferentially expressed in both TMC4 and vEC subsets, suggesting that these cells may contribute to the formation of a local S1P gradient within mEFAs. These findings suggest that mEFAs may be specialized medullary niches associated with stromal organization, the localization of mature thymocytes, and thymic egress.
Related
- An improved protocol to isolate enriched immune cells from murine intestinal epithelium and lamina propria
- The effect of two distinct viral-enriched inocula on the immune response and chemical cues of honey bee pupae
- Task-optimized neural networks reveal distinct contributions of specialized and broader visual learning to neural representations of face familiarity
- Distinct core minor pilin complexes prime specialized type IV filaments in cyanobacteria
- The maternal–fetal interface is an early hematopoietic niche enriched in distinct erythro-myeloid progenitors
BibTeX
@article{sawanobori2026medullary,
title = {{Medullary epithelium-free areas in the rat thymus are specialized niches enriched for mature thymocytes and distinct stromal subsets}},
author = {Yasushi Sawanobori and Tadayuki Ogawa},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1945985},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1945985/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Medullary epithelium-free areas in the rat thymus are specialized niches enriched for mature thymocytes and distinct stromal subsets
AU - Yasushi Sawanobori
AU - Tadayuki Ogawa
PY - 2026
DA - 2026/10/14
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1945985
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1945985/full
AB - The thymic medulla provides the microenvironment for negative selection, late thymocyte maturation, and thymocyte egress, and is generally characterized by widespread distribution of medullary thymic epithelial cells (mTECs). In contrast, the rat thymic medulla contains medullary epithelium-free areas (mEFAs), but the cellular composition and functional significance of these regions remain unclear. Here, to address these questions, we combined spatial transcriptomic data with thymocyte and stromal scRNA-seq reference datasets using robust cell-type decomposition (RCTD) to characterize mEFAs. These analyses revealed that more mature phenotypes within the CD4SP, CD8SP, and regulatory T-cell lineages were preferentially localized in mEFAs, whereas immature SP subsets were enriched in medullary epithelium-containing areas. The newly identified rat thymic mesenchymal cell subsets TMC3 and TMC4 were also enriched in mEFAs. These subsets were broadly similar to mouse medullary fibroblasts but displayed distinct predicted interactions with SP thymocytes, including costimulatory molecule–receptor, chemokine–receptor, and ECM–integrin axes. In addition, venous endothelial cells (vECs) expressing portal endothelial cell markers were enriched in mEFAs. Spns2 , which encodes a transporter that releases S1P from cells into the extracellular space, was preferentially expressed in both TMC4 and vEC subsets, suggesting that these cells may contribute to the formation of a local S1P gradient within mEFAs. These findings suggest that mEFAs may be specialized medullary niches associated with stromal organization, the localization of mature thymocytes, and thymic egress.
SN - 1664-3224
ER -