GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326310/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326310GEOGSEfalseEpCAM identifies a developmentally poised DN thymocyte subset that drives T-cell productionThe 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.2026/04/04GSE326310GSM9628958GSM9628955GSM9628956GSM962895734290326310Mus musculus