Center for Epigenomics of the Mouse Brain Atlas (CEMBA)

小鼠大脑图谱表观基因组学中心 (CEMBA)

• 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
• 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

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：项目摘要 全面了解横跨整个大脑的神经回路是如何产生完整的 感知和行为需要一份脑细胞类型的列表，以及按顺序针对每种细胞类型的方法 询问引起整个系统紧急特性的功能相互作用。至 为应对这些挑战，《鼠脑图谱表观基因组学研究中心》(CEMBA)将重点关注 “表观遗传学图谱”，用于哺乳动物大脑的识别、编目、表征和基因靶向 细胞类型，一种补充RNA表达分析的方法。该中心将开展一项 一套综合的实验，这些实验一起将有助于识别、表征和使基因可获得， 整个神经系统的细胞类型。整个大脑中将有100多万个单一神经元 受到单细胞表观遗传学特征的影响。从这些轮廓中出现的细胞类型将与解剖学联系起来 以详细描述它们的位置、形态以及全脑连接和投影。和 基因图谱数据将被用来生成针对基因表达的工具，并询问 单元类型。通过专注于表观遗传学特征，该中心将利用基因调控知识 识别细胞类型特定遗传增强子的机制。就像在以前的努力中一样 在基因表达谱的基础上产生小鼠品系，工作将包括自下而上和顶部 向下靠近。细胞类型的连通性/解剖学方面的差异知识将用于 表观遗传学特征要与解剖学联系起来。了解细胞群体之间的表观遗传差异将 用于识别增强子，它将基因表达限制在随后将是 受到详细描述的影响。CEMBA-数据核心将收集、管理、分析、可视化和 分发脑细胞类型和解剖数据。最后，行政核心将有效地协调 在脑细胞普查网络中，中心内和合作中心之间的活动。