An Atlas of Human Brain Cell Variation

人类脑细胞变异图谱

基本信息

批准号：
10704184
负责人：
Evan Z Macosko
金额：
$ 1189.31万
依托单位：
BROAD INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-13 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10704184
关键词：
ATAC-seq Acute Adult Alleles Area Atlases Biodiversity Biological Biological Process Biology Brain Brain Diseases Cell Nucleus Cells Complex Creativeness Data Data Analyses Disease Empathy Equipment and supply inventories Exhibits Gene Expression Genes Genetic Genetic Predisposition to Disease Genetic Risk Genetic Variation Genomic Segment Genomics Goals Human Human Genetics Human body Humanities Individual Learning Machine Learning Measurement Measures Mental disorders Molecular Neuroanatomy Neurodevelopmental Disorder Pattern Persons Phenotype Physiology Problem Solving Process Regulator Genes Regulon Resolution Sampling Shapes Slice Slide Spatial Distribution Specimen Structure Tissues Unmarried person Variant Vulnerable Populations Work brain cell brain tissue cell type data resource experience insight inter-individual variation molecular dynamics molecular shape nervous system disorder neuroimaging neuropsychiatric disorder new technology postnatal development postnatal human programs scaffold single nucleus RNA-sequencing transcription factor transcriptomics translational neuroscience

项目摘要

PROJECT SUMMARY/ABSTRACT The human brain exhibits profound diversity in biological function and vulnerability to disease. Despite the biomedical and cultural importance of inter-individual variation, we know relatively little about its underlying cellular and molecular substrates. In this work we will leverage new technologies in single-cell and spatial genomics to construct an Atlas of Human Brain Cell Variation. We will analyze tens of millions of cells from more than 200 people by single-nucleus RNA-seq and single-nucleus ATAC-seq, and a subset of these by spatial transcriptomics. Analysis of these data will seek to understand: the static versus dynamic molecular and spatial features of each cell type; the ways in which human genetic variation shapes the molecular repertoire of each cell type; and the constellations of cellular and molecular features that co-vary, appearing together in the same brains. We seek especially with this work to understand the functional connections between these phenotypes and: (i) the gene regulatory processes that drive and shape it; (ii) genetic variation associated with brain diseases; and (iii) structural brain variation measured in hundreds of neuroimaging studies. The project will deliver an essential data resource for cellular, molecular, genetic and translational neuroscience – while expanding our understanding of the ways the human brain varies across different people.

项目摘要/摘要人脑在生物学功能和疾病脆弱性方面表现出深远的多样性。尽管有个体间变化的生物医学和文化重要性，我们对其潜在的了解相对较少细胞和分子底物。在这项工作中，我们将利用单细胞和空间中的新技术基因组学以构建人类脑细胞变异的地图集。我们将分析更多的细胞单核RNA-seq和单核ATAC-SEQ的200人超过200人，其中一部分是空间的转录组学。这些数据的分析将寻求理解：静态和动态分子和空间每种单元格的功能；人类遗传变异塑造每种分子库的方式细胞类型；以及共同出现的细胞和分子特征的星座大脑。我们特别寻求这项工作以了解这些表型之间的功能联系和：（i）驱动和塑造它的基因调节过程；（ii）与大脑相关的遗传变异疾病；（iii）在数百种神经影像学研究中测量的结构性大脑变异。该项目将为细胞，分子，遗传和翻译神经科学提供必需的数据资源 - 而扩展我们对人脑在不同人群中变化的方式的理解。