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ENSMAP: Molecular and Functional Mapping of the Enteric Nervous System

ENMAP：肠神经系统的分子和功能图谱

基本信息

批准号：
9531523
负责人：
E Michelle SOUTHARD-SMITH
金额：
$ 29.31万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-27 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9531523
关键词：
Adult Anatomy Atlases Biological Assay Bladder Blood Vessels Catalogs Cells Cellular Morphology Collaborations Complement Complex Congenital Megacolon Data Data Set Databases Defecation Development Diabetic Neuropathies Diet Dilatation - action Disease Documentation Electrodes Electrophysiology (science)Enteral Enteric Nervous System Excision Female Fluorescence-Activated Cell Sorting Foundations Frequencies Ganglia Gastric Emptying Gastrointestinal Motility Gene Expression Gene Mutation Genes Genetic Goals Health Human Image Immunohistochemistry In Situ Inbred Strain Inbred Strains Mice Inflammatory disease of the intestine Intestinal Motility Intestines Label Large Intestine Maps Measures Methods Microelectrodes Molecular Molecular Profiling Mouse Strains Movement Mus Neuroanatomy Neurobiology Neurons Nuclear Operative Surgical Procedures Organ Pattern Perfusion Peristalsis Pharmacologic Substance Pharmacology Phenotype Physiological Physiology Positioning Attribute Process Property Proteins Research Personnel Resolution Scientist Small Intestines Stem cells Surveys System Technology Transgenes Transgenic Mice Variant Work base cell motility cell type deep sequencing feeding fetal gene complementation human data immunohistochemical markers laser capture microdissection live cell imaging male man member migration motility disorder mouse model nutrient absorption phenome progenitor public health relevance relating to nervous system response transcriptome transcriptome sequencing treatment planning

项目摘要

PROJECT SUMMARY Gastrointestinal (GI) motility and defecation are absolute prerequisites for nutrient absorption, fecal elimination and overall health. Normal GI motility, vascular perfusion, and intestinal inflammation are coordinated by vast numbers of neurons that reside within ganglia of the enteric nervous system (ENS) intrinsic to the gut wall. While recent work has identified diverse genes that direct the initial development of progenitor cells that give rise to enteric neurons in the wall of the intestine, we know very little about the genes that are expressed in adult enteric neurons. Consequently we are unable to determine whether efforts to generate enteric neurons produce the normal complement of cell types. Moreover we do not fully understand how distinct types of neurons contribute to overall coordination of intestinal motility because the use of common immunohistochemical markers alone does not distinguish functionally distinct subtypes. As a result, our abilities to target and functionally manipulate specific types of neurons in the gut are extremely limited. To surpass these limitations, our application proposes to develop a comprehensive, single cell transcriptome map of adult enteric neurons in normal mice in parallel with deep sequencing of enteric ganglia from distinct regions of human intestine so that a global gene expression atlas of human enteric ganglia is obtained. To capture mouse enteric neurons for single cell RNA-Seq we will use a fluorescent transgenic mouse line that we developed for live-cell imaging of enteric neurons. Human enteric ganglia will be collected by laser capture microdissection from adult surgical remnants. Comparison of enteric neuron expression profiles between mouse and human data sets will identify conserved genes that mark distinct neuronal subtypes. The resulting expression atlas of enteric neurons will define specific molecular fingerprints for discrete neuron subtypes that are essential to pursue targeted, functional manipulation of GI motility in distinct regions of the intestine.

项目总结