权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Classification of Cortical Neurons by Single Cell Transcriptomics

单细胞转录组学对皮质神经元的分类

基本信息

批准号：
8935936
负责人：
JOHN J. NGAI
金额：
$ 145.66万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
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：
2014-09-26 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8935936
关键词：
Anatomy Atlases BRAIN initiative Base of the Brain Behavior Biological Biological Models Biology Brain Brain Mapping Brain region Cataloging Catalogs Cell Separation Cell physiology Cells Cellular Morphology Censuses Classification Classification Scheme Clustered Regularly Interspaced Short Palindromic Repeats Cognition Complement Complex Conscious DNA Sequence Development Emotions Equipment and supply inventories Fingerprint Future Gene Expression Gene Expression Profile Generations Genes Genetic Genetic Techniques Genetically Engineered Mouse Genome Genome engineering Genotype Goals Health Human In Situ Individual Label Location Logic Maps Mediating Memory Methods Molecular Molecular Profiling Morphology Motor output Mouse Strains Movement Mus Nervous System Physiology Neuroglia Neurons Neurosciences Organ Organism Pattern Physiological Physiology Population Process Property Proteins Pyramidal Cells RNA Reporter Research Resources Role Sampling Sensory Sensory Process Somatosensory Cortex Staging Statistical Methods Surface Taxonomy Technology Testing Tissues Transgenic Mice Transgenic Organisms Validation base cell type differential expression hippocampal pyramidal neuron insight molecular marker neural circuit optogenetics recombinase research study scale up single cell sequencing technology development tool transcriptomics

项目摘要

DESCRIPTION (provided by applicant):Unraveling the complexity of the mammalian brain is one of the most challenging problems in biology today. A major goal of neuroscience is to understand how circuits of neurons and non-neuronal cells process sensory information, generate movement, and subserve memory, emotion and cognition. Elucidating the properties of neural circuits requires an understanding of the cell types that comprise these circuits and their roles in processing and integrating information. However, since the description of diverse neuronal cell types over a century ago by Ramon y Cajal, we have barely scratched the surface of understanding the diversity of cell types in the brain and how each individual cell type contributes to nervous system function. Current approaches for classifying neurons rely upon features including the differential expression of small numbers of genes, cell morphology, anatomical location, physiology, and connectivity - important descriptive properties that nonetheless are insufficient to fully describe or predict the vast number of different cell types that comprise the mammalian brain. Here we propose a suite of technologies for identifying and classifying the myriad cell types present in the brain. Our method will be developed using layer 5 pyramidal cells from mouse somatosensory cortex as a model system. First, we will exploit the latest developments in DNA sequencing technologies to characterize gene expression profiles on single layer 5 neurons at high throughput. This information will be used to classify individual cells based on their transcriptome "fingerprints." Second, genes found to define newly discovered neuronal subtypes will be used to gain genetic access to these cells using Cas9/CRISPR-mediated genome engineering to create transgenic reporter lines. Development of this technology promises to open a pipeline for the rapid generation of multigenic mouse reporter strains in which specific neuronal subtypes are uniquely labeled by combinations of tagged genes. Third, we will use these genetically engineered mice to confirm that our taxonomy represents distinct functional properties of the classified neurons. Our approach can ultimately be scaled up to generate a complete census of cell types in the brain, a critically needed resource for dissecting nervous system function with modern investigative tools.