Center for Epigenomics of the Mouse Brain Atlas (CEMBA)

概述：项目摘要 全面了解跨越整个大脑的神经回路是如何产生 感知和行为需要一系列脑细胞类型，以及按顺序瞄准每种细胞类型的方法 去探究那些导致整个系统涌现特性的功能性相互作用。到 为了应对这些挑战，“小鼠大脑图谱表观基因组学中心”（CEMBA）将专注于 “表观遗传分析”，用于哺乳动物大脑的鉴定、编目、表征和遗传靶向 细胞类型，一种与RNA表达分析互补的方法。该中心将开展一项 一系列综合实验，共同用于确定、表征和提供遗传可及性， 整个神经系统的细胞类型。整个大脑中超过100万个单个神经元将被 进行单细胞表观遗传分析。从这些档案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、形态和全脑连接和投射。和 遗传分析数据将用于生成工具，以靶向基因表达并询问以下基因的作用： 细胞类型。通过专注于表观遗传分析，该中心将利用基因调控的知识， 识别细胞类型特异性遗传增强子的机制。正如以前的努力一样， 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自上而下 向下接近。将使用细胞类型的连接性/解剖学差异的知识， 表观遗传图谱与解剖学联系起来。了解细胞群体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激活的神经元群体中。 进行详细的描述。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，行政核心将有效协调 活动中心内和合作中心之间的脑细胞普查网络。

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.