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Single-cell transcriptomics of pituitary stem cell-derived organoid model

ABSTRACT: Single-cell transcriptomics of pituitary stem cell-derived organoid model

PROVIDER: PRJEB74916 | ENA |

REPOSITORIES: ENA

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Single-cell transcriptomics of pituitary stem cell-derived organoid model

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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.

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Project description:Organ architecture is established during development through specific cell:cell contacts. The mechanisms responsible for these specific cell interactions remain poorly understood. In order to address this question, we used the anterior pituitary gland that harbors five different and interdigitated hormone-secreting homotypic cell networks. We now report that blocking differentiation of the first lineage to arise during pituitary development, the corticotrope cells, leads to pituitary hypoplasia with a major effect on the somatotrope cells that are fewer, with less secretory granules and a loss of cell polarity. These somatotrope cell phenotypes are dependent on gene dosage for the corticotrope-restricted transcription factor Tpit. In addition, the Tpit-deficient pituitary is hyper-vascularized. Single cell transcriptomics identifiy corticotrope and somatotrope regulatory and signaling pathways that may underlie cell:cell communications responsible for these phenotypes. Collectively, the results indicate that the corticotrope cell network is an important paracrine signalling center regulating pituitary architecture and size.

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