Project description:The obesity incidence is increasing worldwide with the urgent need to identify new therapeutics. Obesity is associated with endocrine alterations, arising from changes in the hypothalamic-pituitary hormone axes, leading to reproductive disorders, altered basal metabolism and stress hormone production. The focus of this study was to determine if diet induced obesity alters pituitary gland plasticity, gene expression and hormone production and secretion. Here we performed single cell RNA-sequencing (scRNA-seq) on pituitary glands from control (CTRL) and high fat diet (HFD) fed males and looked at cell type population dynamics and gene expression changes between HFD and CTRL for all hormone-producing cell types. Our study revealed diet-induced changes in pituitary gland plasticity and hormone production that may play a role in altered hormone production in obese patients and consequently, dysregulation of pituitary gland homeostasis.
Project description:Macrophages were identified in the pituitary gland long ago, but until recently, we lacked the resolution to comprehensively profile the pituitary gland macrophage compartment. To address this, we examined the developmental kinetics and distinctive characteristics of pituitary macrophages within the developing and homeostatic gland. Whole pituitary glands were collected from newborn (NB) to adult (8 weeks old) wild-type (WT) mice. Our analysis revealed diverse macrophage subsets with marked differences in gene expression profiles and spatial localization, undergoing dynamic phenotypic changes from neonatal stages to adulthood. We observed distinct transcriptional profiles between macrophage subpopulations in the anterior and posterior lobes, underscoring significant molecular divergences. Fate-mapping analyses showed that pituitary macrophages originate from early yolk sac precursors and persist throughout life primarily through local proliferation, even under pathophysiological conditions.
Project description:Macrophages were identified in the pituitary gland long ago, but until recently, we lacked the resolution to comprehensively profile the pituitary gland macrophage compartment. To address this, we examined the developmental kinetics and distinctive characteristics of pituitary macrophages within the developing and homeostatic gland. Whole pituitary glands were collected from newborn (NB) to adult (8 weeks old) wild-type (WT) mice. Our analysis revealed diverse macrophage subsets with marked differences in gene expression profiles and spatial localization, undergoing dynamic phenotypic changes from neonatal stages to adulthood. We observed distinct transcriptional profiles between macrophage subpopulations in the anterior and posterior lobes, underscoring significant molecular divergences. Fate-mapping analyses showed that pituitary macrophages originate from early yolk sac precursors and persist throughout life primarily through local proliferation, even under pathophysiological conditions.
Project description:NR5A1 is expressed in the pituitary gonadotropes and regulates their functional differentiation. We have previously identified a pituitary-specific enhancer region located in the 6th intron of the Nr5a1 gene. In this study, deletion of the pituitary enhancer by genome editing abolished the expression of NR5A1 in the pituitary gland, confirming the functional importance of the enhancer. Transcriptomic changes in the enhancer-deleted mouse pituitary were revealed in both males and females.