Mathematical Modeling of Neurons and Endocrine Cells

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

We are continuing our work with the Stojilkovic lab and the Genomics core of NICHD, providing bioinformatic support for their to single-cell RNAseq analyses of gene expression in the anterior pituitary. This gland is composed of five hormone producing cell types, glia-like folliculostellate cells, and endothelial and blood cells comprising the pituitary sinusoidal capillary network. Some key lines of inquiry in pituitary physiology include three-dimensional organization tissue organization and intercellular communication among cells, development and regeneration of pituitary cells, and the heterogeneity and function of the multiple cell types in the pituitary. The pituitary gland is a complex organ consisting of several hormone-producing cell (HPC) and non-hormonal cell types. Here, we used scRNAseq to characterize the transcriptome profiles of rat pituitary cells. HPC were highly differentiated cells, identified by common expression of dense core secretory vesicle protein genes, and the cell type-specific expression of genes encoding hormones and G protein-coupled receptors. No evidence was found for the existence of multihormonal/multireceptor types of cells. A common feature of S100a-expressing non-hormonal folliculostellate cells (FSC), pituicytes, pericytes, and endothelial cells is their role in the pituitary gland organization. FSC are heterogeneous, composed of a larger FSC1 and smaller FSC2 subclusters, pointing to their specific functions, including the FSC2-specific expression of tight junction genes. FSC1, FSC2, and pituicytes showed high astroglia-like gene signature, some shared, such as S100b, and others distinct. Sox2 was also expressed in most FSC1, FSC2, and pituicytes. In contrast, Prop1 and Prrx1 are expressed in FSC1 and FSC2, and Lhx2 and Tbx3 in pituicytes only. These results indicate the cell-type-specific differentiation of HPC, genetic and functional similarity between FSC and pituicytes, and the potential roles of FSC2 in stem-cell niche function and pericytes/endothelial cells in pituitary functions other than blood supply. A paper is in preparation and will be discussed in a future report.