PT  - JOURNAL ARTICLE
AU  - Yugong Ho
AU  - Peng Hu
AU  - Michael T. Peel
AU  - Pablo G. Camara
AU  - Hao Wu
AU  - Stephen A. Liebhaber
TI  - Single cell transcriptomic analysis of the adult mouse pituitary reveals a novel multi-hormone cell cluster and physiologic demand-induced lineage plasticity
AID  - 10.1101/475558
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 475558
4099  - http://biorxiv.org/content/early/2018/11/22/475558.short
4100  - http://biorxiv.org/content/early/2018/11/22/475558.full
AB  - The anterior pituitary gland drives a set of highly conserved physiologic processes in mammalian species. These hormonally-controlled processes are central to somatic growth, pubertal transformation, fertility, lactation, and metabolism. Current models, based on targeted 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 a more complex model in which critical aspects of hormone specificity and plasticity of pituitary cells remain undefined. Here we have applied massively parallel single-cell RNA sequencing (scRNA-seq), in conjunction with a set of orthogonal imaging studies, to systematically map the cellular composition of adult male and female mouse pituitaries at single-cell resolution and in the setting of major physiologic demands. These analyses reveal sex-specific cellular diversity associated with normal pituitary homeostasis, and identify an array of specific hormone-enriched cell-types and a series of non-hormone producing interstitial and supporting cell lineages. Unexpectedly, scRNA-seq further uncovers the presence of a major cell cluster that is characterized by a unique multi-hormone gene expression profile. The detection of dynamic shifts in cellular representations and transcriptome profiles within a number of these clusters in response to well-defined physiologic demands suggests their corresponding roles in cellular plasticity. These studies point to an unanticipated complexity and plasticity in pituitary cellular composition that may serve to expand upon current models and concepts of pituitary hormone gene expression.