Carmn sustains basal stemness in exocrine glands and CTND1-mediated Wnt signaling in mammary tissue

Abstract Exocrine glands, despite varied secretory functions and locations, share similar structures and stem cell-dependent development and regeneration. However, the common stem cell regulatory mechanisms across these glands remain elusive. In this study, we integrate single-cell RNA sequencing datasets from mammary, salivary, and lacrimal glands across species and discover the specific enrichment of the long noncoding RNA Carmn in epithelial stem cell-enriched basal lineages. Functional studies demonstrate that Carmn regulates progenitor cell activity and the plasticity of basal cells in exocrine glands. In the mammary gland, Carmn regulates the Wnt/β-Catenin-driven stem cell program through an interaction with CTND1. Furthermore, Carmn is required for tumor formation by Wnt1-driven tumor stem cells. Together, these findings identify Carmn as a conserved regulator of epithelial basal-cell stemness in exocrine glands and as a facilitator of Wnt/β-catenin signaling.