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EpCAM identifies a developmentally poised DN thymocyte subset that drives T-cell production

ABSTRACT: The age-related decline in thymic function is a major contributor to immune senescence. While stromal degeneration is a known cause, the intrinsic heterogeneity and regulatory mechanisms within early thymocyte progenitors are poorly understood. Here, we report that the epithelial cell adhesion molecule (EpCAM), conventionally a marker of thymic epithelial cells, identifies a functionally distinct subset within double-negative (DN) thymocytes. EpCAM⁺ DN cells are transcriptionally and epigenetically primed for T-cell lineage commitment, exhibit superior proliferative and differentiation potential in vitro, and serve as the dominant precursors for T-cell reconstitution in vivo. This progenitor pool expands acutely following thymic injury but undergoes pronounced contraction with age, a trajectory conserved in the human thymus. Our findings redefine EpCAM as a marker of a developmentally competent DN thymocyte state, whose erosion contributes to thymic involution and presents a potential target for regenerative strategies.

ORGANISM(S): Mus musculus

PROVIDER: GSE326310 | GEO | 2026/04/04

REPOSITORIES: GEO

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EpCAM identifies a developmentally poised DN thymocyte subset that drives T-cell production

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