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Epigenomic cell-type classification and regulatory element identification in the human brain

人脑表观基因组细胞类型分类和调控元件鉴定

基本信息

批准号：
10018649
负责人：
M MARGARITA BEHRENS
金额：
$ 179.11万
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：
2019
资助国家：
美国
起止时间：
2019-09-16 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10018649
关键词：
ATAC-seq Age Algorithms Atlases BRAIN initiative Behavioral Brain Brain region Categories Cell Nucleus Cells Censuses Chromatin Classification Communities Complex Consensus Cytosine DNA DNA Methylation DNA analysis Data Data Set Development Dissection Distal Enhancers Female Freezing Gene Expression Profile Genetic Fingerprintings Genome Genomics Goals Human Immunohistochemistry In Situ Hybridization Individual Institutes Joints Location Mental disorders Methylation Mitotic Molecular Mus National Institute of Mental Health National Institute of Neurological Disorders and Stroke Nature Neuroglia Neurons Nucleic Acid Regulatory Sequences Parvalbumins Phase Physiological Production RNA Regulator Genes Regulatory Element Research Research Personnel Resolution Schizophrenia Science Single Nucleotide Polymorphism Specimen Techniques Tissues Validation autism spectrum disorder base brain cell brain tissue cell type computational pipelines data integration epigenome epigenomics excitatory neuron experience frontal lobe genetic analysis genetic variant genome wide association study genome-wide human disease inhibitory neuron male methylome multimodal data multimodality nervous system disorder neural circuit neurochemistry predictive marker single cell analysis single-cell RNA sequencing tool transcriptome transcriptomics

项目摘要

Abstract Understanding the exact cell-type composition in the different regions of the human brain is a fundamental step when trying to integrate physiological, behavioral, neurochemical and molecular data. At present, although major categories of cell-types present in the human brain have been defined through a handful of specific markers, the different subtypes within these categories as well as their location are far from understood. Cytosine DNA methylation (mC) is a stable epigenomic signature that persists in post-mitotic cells throughout their lifetime, defining their cellular identity. Open chromatin marks gene regulatory elements that control cell type-specific gene expression patterns. Single cell DNA methylation and open chromatin profiles have been successfully used to identify de novo distinct cell types in heterogeneous tissues including the brain. This U01 aims to produce a first version of an epigenomic cell atlas at the single-cell level across the human brain. Multi-modal integration between epigenomic and transcriptomic signatures will allow the identification of new cell types and unique cell-type markers that will become available to the community. Epigenomic profiling of human brain cells permits the discovery of cell type-specific regulatory regions, which will facilitate the functional analysis of genetic variants associated with psychiatric and neurological disorders.

摘要了解人类大脑不同区域的确切细胞类型组成是一个基本步骤当试图整合生理、行为、神经化学和分子数据时。目前，尽管人类大脑中存在的主要细胞类型已经通过一些特定的虽然这些标记物的种类很多，但这些类别中的不同亚型以及它们的位置还远未被理解。胞嘧啶DNA甲基化（mC）是一种稳定的表观基因组标记，在整个细胞周期中持续存在于有丝分裂后的细胞中。开放的染色质标志着控制细胞的基因调控元件，单细胞DNA甲基化和开放染色质谱已经被发现，成功地用于在包括大脑在内的异质组织中重新鉴定不同的细胞类型。目的是在整个人脑的单细胞水平上制作第一版表观基因组细胞图谱。表观基因组和转录组标签之间的多模式整合将允许鉴定新的细胞类型和独特的细胞类型标记，将成为可用的社区。人类脑细胞允许发现细胞类型的特异性调节区域，这将有助于与精神和神经疾病相关的遗传变异的功能分析。