Mathematical Modeling of Neurons and Endocrine Cells

神经元和内分泌细胞的数学模型

• 批准号: 10008647
• 负责人: Arthur Sherman
• 金额: $ 19.66万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10008647
• 关键词: Action Potentials; Anterior Pituitary Gland; Area; Blood Cells; Calcium; Calcium Channel; Cell Adhesion; Cells; Chemicals; Complement; Coupled; Data; Development; Differential Equation; Dimensions; Discontinuous Capillary; Drug Metabolic Detoxication; Endocrine; Endoplasmic Reticulum; Endothelial Cells; Enzymes; Exocytosis; Extracellular Matrix; Female; Functional disorder; Future; Gene Expression; Gene Expression Profiling; Genes; Genetic Markers; Genomics; Gland; Heterogeneity; Hodgkin-Huxley model; Hormones; Hypothalamic structure; Insulin; Investigation; Ligands; Mediating; Mediator of activation protein; Membrane; Modeling; Molecular; National Institute of Child Health and Human Development; Natural regeneration; Nerve; Neuroglia; Neurons; Neurosecretory Systems; Neurotransmitters; Nobel Prize; Organelles; Paper; Physiology; Pituitary Gland; Population; Preparation; Proteins; Rattus; Role; Second Messenger Systems; Signaling Protein; Sister; Solid; Specificity; Stem cells; Structure; Structure of beta Cell of islet; System; Time; Tissues; Work; base; cell type; comparative; intercellular communication; interest; male; mathematical model; novel; pituitary gland development; postnatal; sexual dimorphism; tool; transcriptome; transcriptome sequencing

Together with the Stojilkovic lab and the Genomics core of NICHD, we have initiated a new direction in these studies, single-cell RNAseq analysis 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 folliculostellate cells. Great efforts have been dedicated towards these aims, but many of the molecular underpinnings remain unknown. We have carried out the first single-cell transcriptome study of anterior pituitary cells. We profiled over 6700 freshly dispersed cells from postpubertal male and female rats. In addition to confirming known markers, our transcriptome analysis highlights many novel genetic markers contributing to pituitary cell type identity and sexual dimorphism. We provide for the first time an estimate of the percentage of folliculostellate cells, and we identify at least two main subtypes of this heterogeneous cell population. Our data support the hypothesis that folliculostellate cells provide structural support for the hormone producing cells, as they express many genes encoding detoxification enzymes. Our analysis of expression of developmental, stem cell/progenitor, and neuroendocrine markers suggests that folliculostellate and hormone producing cells are sister cells with a common origin. We also provide a detailed view of cell type-dependent expression of genes encoding extracellular matrix, cell adhesion, and endogenous ligand proteins, critical for the tridimensional organization of the anterior pituitary and the cross-talk between its constituent cells. We expect the marker genes identified for pituitary cell types will serve as a solid base for future investigations into pituitary structure, function, and pathophysiology, as well as for the study of postnatal pituitary development, regeneration, and reorganization. A paper is in press.

与Stojilkovic实验室和NICHD基因组学核心一起，我们在这些研究中开创了一个新的方向，单细胞RNAseq分析垂体前叶基因表达。该腺体由五种激素产生细胞类型，胶质样卵泡星状细胞，内皮细胞和血细胞组成垂体窦毛细血管网络。垂体生理学的主要研究方向包括：三维组织、组织和细胞间通讯、垂体细胞的发育和再生、卵泡星状细胞的异质性和功能。人们为实现这些目标付出了巨大的努力，但许多分子基础仍然未知。