Center for Epigenomics of the Mouse Brain Atlas (CEMBA)

小鼠大脑图谱表观基因组学中心 (CEMBA)

基本信息

批准号：
9568015
负责人：
EDWARD M CALLAWAY
金额：
$ 480.55万
依托单位：
SALK INSTITUTE FOR BIOLOGICAL STUDIES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-20 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9568015
关键词：
Accelerometer Address Anatomy Animals Atlases Behavior Biological Neural Networks Brain Brain region Cataloging Catalogs Cells Censuses Chromatin Classification Complex DNA Methylation Data Distant Engineering Enhancers Epigenetic Process Face Female Foundations Gene Expression Gene Expression Profiling Gene Targeting Genetic Genetic Enhancer Element Genetic Transcription Goals Human Institution Knowledge Laboratory mice Link Location Modeling Molecular Analysis Molecular Genetics Molecular Profiling Monitor Morphology Mus Nervous system structure Neurons Output Perception Pharmacogenetics Population Property Rabies Regulator Genes Regulatory Element Research Role Specificity Subcellular Anatomy System Technology Transgenes Transgenic Organisms Viral adeno-associated viral vector brain cell calcium indicator cell type epigenetic profiling epigenomics experimental study genetic profiling genome-wide human disease insight interest male neural circuit nonhuman primate optogenetics tool transgene expression virus genetics

项目摘要

OVERVIEW: Project Summary A comprehensive understanding of how neural circuits spanning the entire brain generate the full repertoire of perception and behaviors requires a list of brain cell types, as well the means to target each cell type in order to interrogate the functional interactions that give rise to the emergent properties of the whole system. To address these challenges, the “Center for Epigenomics of the Mouse Brain Atlas” (CEMBA) will focus on “epigenetic profiling”, for identification, cataloging, characterization and genetic targeting of mammalian brain cell types, an approach that is complementary to RNA expression analysis. The Center will conduct an integrated set of experiments that together will serve to identify, characterize and make genetically accessible, cell types across the entire nervous system. More than 1 million single neurons across the whole brain will be subjected to single cell epigenetic profiling. Cell types emerging from these profiles will be linked to anatomy for detailed characterization of their locations, morphology, and brain-wide connectivity and projections. And genetic profiling data will be used to generate tools to target gene expression to and interrogate the roles of cell types. By focusing on epigenetic profiling, the Center will harness knowledge of gene regulatory mechanisms to identify cell-type specific genetic enhancers. As has been the case in previous efforts to generate mouse lines on the basis of gene expression profiling, efforts will include both bottom up and top down approaches. Knowledge of differences in the connectivity/anatomy of cell types will be used to allow epigenetic profiles to be linked to anatomy. Knowledge of epigenetic differences between cell populations will be used to identify enhancers, which restrict gene expression to neuronal populations that will be subsequently subjected to detailed characterization. The CEMBA-Data Core will collect, manage, analyze, visualize and distribute brain cell-type and anatomical data. Finally, the Administrative Core will effectively coordinate activities within the center and between cooperating centers in the Brain Cell Census Network.

概述：项目概要全面了解跨越整个大脑的神经回路如何产生完整的指令集感知和行为需要一系列脑细胞类型，以及按顺序针对每种细胞类型的方法询问引起整个系统涌现特性的功能相互作用。为了应对这些挑战，“小鼠大脑图谱表观基因组学中心”（CEMBA）将重点关注 “表观遗传分析”，用于哺乳动物大脑的识别、编目、表征和遗传靶向细胞类型，这是一种与 RNA 表达分析互补的方法。一套综合的实验，这些实验将共同用于识别、表征和使遗传可及性，整个神经系统的细胞类型将超过 100 万个单个神经元。从这些图谱中得出的细胞类型将与解剖学相关联。详细描述它们的位置、形态以及全脑连接和预测。基因分析数据将用于生成工具来定位基因表达并询问其作用通过关注表观遗传分析，该中心将利用基因调控知识。识别细胞类型特异性遗传增强子的机制正如之前的努力一样。根据基因表达谱生成小鼠品系，工作将包括自下而上和自上而下细胞类型的连接/解剖学差异的知识将用于允许。与解剖学相关的表观遗传特征将有助于了解细胞群之间的表观遗传差异。用于识别增强子，其将基因表达限制在随后将被 CEMBA-Data Core 将进行详细的表征。最后，管理核心将有效协调分发脑细胞类型和解剖数据。中心内部以及脑细胞普查网络合作中心之间的活动。