Introduction: . The adrenal glands are central regulators of endocrine homeostasis and stress adaptation. Despite decades of research, the molecular mechanisms governing adrenal zonation and cortical renewal remain incompletely understood.
Material and methods: . Here, the 10x Genomics Visium CytAssist platform was applied to generate a high-resolution atlas of the adult CD1 IGS male mouse adrenal gland. The study employed a range of analytical approaches, including unsupervised clustering, differential gene expression analysis, pathway and Gene Ontology enrichment, cell-type deconvolution, and pseudotime trajectory inference. These approaches collectively facilitated the comprehensive characterization of transcriptional signatures across the primary adrenal cortical zones and the medulla.
Results: . Herein transcriptional signatures of distinct compartments were identified, including zona glomerulosa/adrenal capsule (ZG/capsule), outer and inner zona fasciculata (oZF, iZF), medulla, connective tissue, and surrounding brown and white adipose depots. Deconvolution analysis further delineated contributions from stromal, immune, endothelial, and erythrocyte populations, highlighting the complexity of adrenal and periadrenal tissues. Pseudotime trajectory analysis validated the centripetal differentiation model of the adrenal cortex, demonstrating a continuum of transcriptional states from capsule and ZG/capsule through oZF to iZF, consistent with progressive acquisition of steroidogenic functions. Functional enrichment confirmed zone-specific pathways, including WNT and steroid biosynthesis in the cortex and neuroendocrine pathways in the medulla.
Conclusions: . Together, this study provides the first spatially resolved transcriptomic reference map of the adult male mouse adrenal gland, revealing the cellular and molecular framework underlying zonation, renewal, and inter-compartment interactions. This atlas constitutes a valuable resource for advancing the understanding of adrenal physiology and pathology.
Keywords: adrenal gland; adrenal zonation; centripetal differentiation; gene expression; spatial transcriptomics; transcriptomic atlas.