Single Cell Analysis of Salt Transduction

盐转导的单细胞分析

基本信息

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
项目类别：
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

项目摘要

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/水平衡对哺乳动物生理学至关重要。盐的过度消费与健康问题，尤其是高血压有关。盐味替代品或增强剂的发展部分是由于对受体的不完全了解以及负责盐味的其他信号转导成分的知识。尽管已显示上皮钠通道参与了对艾米洛里德敏感的盐味转导，但艾米洛里德无敏感（AI）盐味道转导机制仍有待阐明。这项拟议的研究的目的是通过识别AI盐转导成分来提高我们对盐味的理解。我们将在功能上表征味蕾细胞，并分别识别并单独收集AI盐反应性II型苦受体细胞和AI盐III型味蕾味芽细胞以及对照CELS盐无反应II型和III型细胞（AIM 1）。我们将使用深层测序对这些单细胞的转录组进行扩增和询问，并确定在盐响应性AI II型和III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，以鉴定候选AI盐受体基因（AIM 2）。这些候选基因在AI盐味中的作用将在我们的后续研究。这些研究的结果可以填补理解盐味和感知的重要空白，从而导致有效的方法减少盐的消耗。