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An Atlas of Human Brain Cell Variation

人类脑细胞变异图谱

基本信息

批准号：
10523654
负责人：
Evan Z Macosko
金额：
$ 1490.72万
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/10523654
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 Individual Learning Machine Learning Measurement Measures Mental disorders Molecular Molecular Genetics 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 base brain cell brain tissue cell type data resource experience insight inter-individual variation molecular shape nervous system disorder neuroimaging neuropsychiatric disorder new technology postnatal development postnatal human programs scaffold transcription factor transcriptome sequencing 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/摘要人类大脑在生物功能和对疾病的脆弱性方面表现出深刻的多样性。尽管个体间变异的生物医学和文化重要性，但我们对其潜在原因知之甚少细胞和分子底物。在这项工作中，我们将利用单细胞和空间领域的新技术基因组学构建人脑细胞变异图谱。我们将分析来自更多的数千万个细胞单核rna-seq和单核atac-seq的200多人，以及其中的一个子集的空间分布转录学。对这些数据的分析将试图理解：静态与动态分子和空间每种细胞类型的特征；人类遗传变异如何塑造每种细胞的分子谱系细胞类型；以及共同变化的细胞和分子特征的星座，一起出现在同一大脑。我们特别试图通过这项工作来理解这些表型之间的功能联系。以及：(I)驱动和塑造它的基因调控过程；(Ii)与大脑相关的遗传变异疾病；以及(Iii)在数百项神经成像研究中测量到的大脑结构变异。该项目将提供细胞、分子、遗传和翻译神经科学的基本数据资源-同时扩大了我们对人脑在不同人之间变化方式的理解。