权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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：
10248439
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 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10248439
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 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：了解人类大脑的三个不同区域中最准确的细胞型细胞组成是非常重要的一步。当我试图将生理、行为、神经化学和分子生物学数据整合在一起时，尽管目前还没有。目前人类大脑中存在的几种主要细胞类型还没有通过几种特定的细胞类型来定义。标记物，以及这些类别中的三个不同的亚型，以及它们的位置信息，还远未被理解。胞嘧啶脱氧核糖核酸甲基化基因(MC)是一种非常稳定的表观基因组特征，它在整个有丝分裂后的干细胞中持续存在。他们的一生，定义了他们最重要的细胞身份。染色质开放标志着控制细胞的基因和调控元件。特定类型基因的表达模式。单个核细胞的DNA甲基化和开放的染色质谱尚未见报道。成功地利用这一技术识别了包括大脑在内的各种不同组织中的新生细胞和不同的细胞类型。其目标是在整个人类大脑皮层的第一个单细胞水平上，成功地制作出首个完整的表观基因组基因组图谱。表观基因组学和转录基因组学签名之间的多模式信息整合将使我们能够更好地识别新的基因。细胞类型和独特的细胞类型标记表明，它们将成为未来社区的可用工具。人类脑组织细胞允许发现特定细胞类型的基因调控区域，这将进一步促进这一进程。对这些基因变异的功能分析表明，它们与精神疾病和神经功能障碍有关。