Single Cell Analysis of Salt Transduction

盐转导的单细胞分析

• 批准号: 8788399
• 负责人: LIQUAN HUANG
• 金额: $ 21.95万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8788399
• 关键词: Amiloride; Avidity; Bioinformatics; Ca(2+)-Transporting ATPase; Calcium; Candidate Disease Gene; Cations; Cells; Collecting Cell; Consumption; Cycloheximide; Development; Electrophysiology (science); Enhancers; Epithelial; Equilibrium; Esthesia; Food; GTP-Binding Proteins; Gene Expression Profile; Genes; Goals; Grant; Health; Human; Hypertension; Image; Immunohistochemistry; In Situ Hybridization; Individual; Ion Channel; Knowledge; Lead; Link; Lithium; Methods; Mus; Nature; Pathway interactions; Perception; Pharmacology; Physiological; Physiology; Protein Subunits; Receptor Cell; Receptor Gene; Reporting; Research; Role; Salts; Signal Transduction; Sodium; Sodium Channel; Sodium Chloride; Solutions; TRPM5 gene; Taste Bud Cell; Taste Buds; Taste Perception; Technology; Transducers; Type III Epithelial Receptor Cell; Validation; Water; base; cell type; cellular imaging; deep sequencing; design; differential expression; epithelial Na+ channel; follow-up; hedonic; high risk; novel strategies; preference; prevent; receptor; response; salt sensitive; screening; selective expression; single cell analysis; taste transduction

DESCRIPTION (provided by applicant): Salt/water balance is crucial to mammalian physiology. Overconsumption of salt has been linked with health problems, particularly hypertension. Development of salt taste substitutes or enhancers has been ineffective partly due to the incomplete knowledge of the receptors and other signal transduction components responsible for salt taste. While an epithelial sodium channel has been shown to be involved in the amiloride-sensitive salt taste transduction, the amiloride-insensitive (AI) salt taste transduction mechanism remains to be elucidated. The goal of this proposed research is to advance our understanding of salt taste by identifying the AI salt transduction components. We will functionally characterize taste bud cells and identify and individually collect AI salt-responsive type II bitter receptor cells and AI salt type III taste bud cells as well as control cels salt-unresponsive type II and III cells, respectively (Aim 1). We will amplify and interrogate thes single cells' transcriptomes using deep sequencing, and identify genes that are preferentially expressed in the salt-responsive AI type II and III cells. We will perform in-depth bioinformatic analysis on these differentially expressed genes to identify candidate AI salt receptor genes (Aim 2). The role of these candidate genes in the AI salt taste will be further investigated in our follow-up studies. Results from these studies can fill an important gap in understanding salt taste sensation and perception, thus leading to effective means to reduce salt consumption.

描述（由申请人提供）：盐/水平衡对哺乳动物的生理至关重要。过度食用盐与健康问题有关，特别是高血压。咸味替代品或增强剂的开发一直是无效的，部分原因是对负责咸味的受体和其他信号转导组分的了解不完全。虽然上皮钠通道已被证明参与阿米洛利敏感的盐味转导，阿米洛利不敏感（AI）盐味转导机制仍有待阐明。这项研究的目标是通过识别AI盐转导成分来促进我们对盐味道的理解。我们将在功能上表征味蕾细胞，并分别鉴定和单独收集AI盐响应II型苦味受体细胞和AI盐III型味蕾细胞以及对照的AI盐不响应II型和III型细胞（目的1）。我们将使用深度测序扩增和询问这些单细胞的转录组，并鉴定在盐响应性AI II型和III型细胞中优先表达的基因。我们将对这些差异表达的基因进行深入的生物信息学分析，以确定候选AI盐受体基因（Aim 2）。这些候选基因在AI咸味中的作用将在我们的研究中进一步研究。 后续研究。这些研究的结果可以填补理解盐的味觉和感知的重要空白，从而导致有效的手段，以减少盐的消费。