Single-cell transcriptomic analysis of adult mouse pituitary reveals sexual dimorphism and physiologic demand-induced cellular plasticity

TLDR

The anterior pituitary regulates essential physiological processes such as growth, puberty, fertility, lactation, and metabolism, and while traditional models assign each hormone to a distinct cell lineage, recent evidence indicates a more complex relationship between hormone specificity and cellular plasticity. The study aims to map cell-type diversity and functional state heterogeneity in adult male and female mouse pituitaries using single‑cell RNA sequencing and complementary imaging under physiological demands. The authors employed massively parallel single‑cell RNA sequencing combined with imaging‑based single‑cell mRNA and protein analyses to systematically profile adult mouse pituitary cells. The analyses revealed sex‑specific pituitary cell composition, diverse hormone‑enriched and non‑hormone‑producing cell types—including a Pou1f1‑expressing multi‑hormone population—and dynamic shifts in cellular diversity and transcriptomes in response to physiological stress, highlighting unexpected cellular complexity and plasticity.

Abstract

Abstract The anterior pituitary gland drives highly conserved physiologic processes in mammalian species. These hormonally controlled processes are central to somatic growth, pubertal transformation, fertility, lactation, and metabolism. Current cellular models of mammalian anteiror pituitary, largely built on candidate gene based immuno-histochemical and mRNA analyses, suggest that each of the seven hormones synthesized by the pituitary is produced by a specific and exclusive cell lineage. However, emerging evidence suggests more complex relationship between hormone specificity and cell plasticity. Here we have applied massively parallel single-cell RNA sequencing (scRNA-seq), in conjunction with complementary imaging-based single-cell analyses of mRNAs and proteins, to systematically map both cell-type diversity and functional state heterogeneity in adult male and female mouse pituitaries at single-cell resolution and in the context of major physiologic demands. These quantitative single-cell analyses reveal sex-specific cell-type composition under normal pituitary homeostasis, identify an array of cells associated with complex complements of hormone-enrichment, and undercover non-hormone producing interstitial and supporting cell-types. Interestingly, we also identified a Pou1f1-expressing cell population that is characterized by a unique multi-hormone gene expression profile. In response to two well-defined physiologic stresses, dynamic shifts in cellular diversity and transcriptome profiles were observed for major hormone producing and the putative multi-hormone cells. These studies reveal unanticipated cellular complexity and plasticity in adult pituitary, and provide a rich resource for further validating and expanding our molecular understanding of pituitary gene expression programs and hormone production.