Olfactory Support Cells

嗅觉支持细胞

• 批准号: 7738592
• 负责人: Timothy S McClintock
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7738592
• 关键词: Abbreviations; Acinar Cell; Afferent Neurons; Aging; Animals; Apoptotic; Binding; Bioinformatics; Biological Process; Cell Adhesion; Cell physiology; Cell secretion; Cells; Chemicals; DNA; Data; Data Set; Databases; Detection; Disease; Environment; Epithelium; Family; Fluorescence-Activated Cell Sorting; Gene Expression; Genes; Gland; Green Fluorescent Proteins; Immune; In Situ Hybridization; Ion Transport; Knock-out; Knowledge; LacZ Genes; Lead; Longevity; Messenger RNA; Molecular; Molecular Profiling; Mouse Strains; Mucous body substance; Mus; Neurons; Odors; Olfactory Epithelium; Olfactory Nerve; Outcome; Pathway interactions; Pattern; Phagocytosis; Probability; Receptor Protein-Tyrosine Kinases; Reporter; Retinal Degeneration; Sampling; Signal Pathway; Signal Transduction; Site; Structure of respiratory epithelium; Supporting Cell; System; Testing; Tissues; Xenobiotics; afferent nerve; age related; axl receptor tyrosine kinase; cell type; directed attention; improved; postnatal; public health relevance; receptor; recombinase; relating to nervous system; reproductive; research study; sustentacular cell

Description (provided by applicant): The support cells of the olfactory epithelium have received little direct attention, yet several lines of evidence indicate that they are critical for maintaining or regulating the olfactory sensory nerve cells, the ongoing replacement of olfactory sensory nerve cells, and the local environment that allows odor detection. A detailed molecular understanding of the two major types of support cells, sustentacular cells and Bowman's gland cells, is lacking. Fortuitously, we have developed a mouse strain that will allow us to extract two dissociated cell samples: One highly enriched for sustentacular cells, the other for Bowman's gland acinar cells. Aim 1 will therefore investigate whether two support cell transcriptomes show overrepresentation of biological processes hypothesized to be active in these support cells: Clearance of foreign chemicals, cell adhesion, clearance of dying cells, secretion, and certain cell signaling pathways. The outcome of this aim will also include a database of the probability of expression in sustentacular cells and Bowman's gland acinar cells for more than 10,000 genes. Aim 2 delves more deeply into a mechanism we hypothesize controls phagocytosis by sustentacular cells, one of the few documented functions of these cells. We hypothesize that signaling through the receptor tyrosine kinase Tyro3 regulates clearance of dying nerve cells by sustentacular cells. Overall, this project is another step toward a complete understanding of gene expression patterns in the olfactory epithelium and will identify most functions present in the little-studied support cells of this tissue. In addition, these experiments are relevant to age-dependent loss of olfactory function because deficits in Tyro3 receptor family signaling in the support cells of several other tissues are known to lead to age-related disorders, such as retinal degeneration. PUBLIC HEALTH RELEVANCE: The olfactory system has evolved to detect and discriminate many thousands of distinct volatile chemicals, in part by generating a favorable microenvironment and retaining the ability to replace damaged olfactory nerve cells even as aging occurs. Investigating how the support cells of the epithelium contribute to odor detection and nerve cell replacement is bound to improve our understanding of how cellular interactions contribute to the ability of the olfactory system to function throughout an animal's life span. This project investigates the molecular capabilities of the support cells of the epithelium and a hypothesized mechanism by which support cells clear dying nerve cells to make way for new nerve cells.

描述（由申请人提供）：嗅觉上皮的支持细胞很少受到直接关注，但有几条证据表明，它们对于维持或调节嗅觉感觉神经细胞、嗅觉感觉神经细胞的持续替换以及允许气味检测的局部环境至关重要。对支持细胞的两种主要类型，支撑细胞和鲍曼腺细胞，缺乏详细的分子理解。幸运的是，我们开发了一种小鼠菌株，使我们能够提取两种分离的细胞样本：一种是高度富集的支撑细胞，另一种是鲍曼腺腺泡细胞。因此，Aim 1将研究两个支持细胞转录组是否过度代表了在这些支持细胞中假设活跃的生物过程：清除外来化学物质、细胞粘附、清除死亡细胞、分泌和某些细胞信号通路。这一目标的结果还将包括一个数据库，其中包含超过10,000个基因在支撑细胞和鲍曼腺腺泡细胞中表达的概率。Aim 2更深入地探讨了一种机制，我们假设通过支撑细胞控制吞噬，这是这些细胞的少数记录功能之一。我们假设通过受体酪氨酸激酶Tyro3的信号传导调节支撑细胞对垂死神经细胞的清除。总的来说，这个项目是朝着完全理解嗅觉上皮基因表达模式迈出的又一步，并将确定存在于该组织中很少研究的支持细胞中的大多数功能。此外，这些实验与年龄依赖性嗅觉功能丧失有关，因为已知几种其他组织支持细胞中Tyro3受体家族信号的缺陷会导致与年龄相关的疾病，如视网膜变性。公共卫生相关性：嗅觉系统已经进化到能够检测和区分数千种不同的挥发性化学物质，部分原因是通过产生有利的微环境，并在衰老发生时保留替换受损嗅觉神经细胞的能力。研究上皮的支持细胞如何参与气味检测和神经细胞替代，将有助于我们更好地理解细胞相互作用如何促进动物整个生命周期中嗅觉系统的功能。本项目研究了上皮支持细胞的分子功能，以及支持细胞清除死亡神经细胞为新神经细胞让路的假设机制。