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的基因组学核心一起，我们在这些研究中开创了一个新的方向，即垂体前叶基因表达的单细胞RNAseq分析。 该腺体由五种激素产生细胞类型、胶质样滤泡星状细胞、以及包括垂体窦毛细血管网的内皮细胞和血细胞组成。垂体生理学的一些关键研究方向包括三维组织结构、组织结构和细胞间通讯、垂体细胞的发育和再生以及滤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。 我们已经进行了第一个单细胞的垂体前叶细胞的转录组研究。我们分析了来自青春期后雄性和雌性大鼠的超过6700个新鲜分散的细胞。除了确认已知的标记，我们的转录组分析突出了许多新的遗传标记，有助于垂体细胞类型的身份和性二型性。我们提供了第一次估计的百分比folliculostellate细胞，我们确定了至少两个主要亚型的这种异质性细胞群体。我们的数据支持这一假设，即滤泡星状细胞为激素产生细胞提供结构支持，因为它们表达许多编码解毒酶的基因。我们对发育、干细胞/祖细胞和神经内分泌标记物表达的分析表明，卵泡星形细胞和激素产生细胞是具有共同起源的姐妹细胞。我们还提供了细胞类型依赖性的细胞外基质，细胞粘附和内源性配体蛋白编码基因的表达，垂体前叶的三维组织和其组成细胞之间的串扰的关键。 我们希望确定的垂体细胞类型的标记基因将作为一个坚实的基础，为未来的调查垂体结构，功能和病理生理学，以及研究出生后垂体的发育，再生和重组。 一篇论文正在印刷中.