Project #2 Integrated single-nucleus multi-omics (ATAC-seq+RNA-seq or chromatin accessibility + RNA-seq) of human TGs

项目

基本信息

批准号：
10806548
负责人：
Hao Wu
金额：
$ 136.43万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-20 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10806548
关键词：
ATAC-seq Atlases Behavioral Biological Assay Biological Markers Biology Cell Nucleus Cells Cellular Assay Chromatin Collaborations Collection Complement Complex Cryopreserved Tissue DNA Methylation Data Data Analyses Data Set Diagnosis Dissociation Drug Targeting Electrophysiology (science)Epigenetic Process Esthesia Evaluation Facial Pain Foundations Gene Expression Gene Expression Profiling Genes Genetic Databases Genetic Transcription Genomics Goals Head Headache Headache Disorders Health Helping to End Addiction Long-term Household Human Human Characteristics International Joints Knowledge Lead Length Maps Measurement Mediating Messenger RNA Methods Methyltransferase Migraine Modality Molecular Morphology Multiomic Data Neuroglia Neurons Nuclear RNA Pain Pain Clinics Patients Physiological Prevalence RNA Regulator Genes Regulatory Element Research Personnel Resolution Resources Sampling Spinal Spinal Ganglia Structure of trigeminal ganglion System Tissues Trigeminal System Uncertainty United States Universities Untranslated RNA Vertebral column allodynia cell type chronic pain chronic painful condition comparative effective therapy epigenome epigenomics gene regulatory network human RNA sequencing in vivo insight migraine treatment multidisciplinary multiple omics nervous system disorder neuronal cell body novel novel strategies response single-cell RNA sequencing somatosensory transcriptome transcriptome sequencing transcriptomics

ATAC-seq Atlases Behavioral Biological Assay Biological Markers Biology Cell Nucleus Cells Cellular Assay Chromatin Collaborations Collection Complement Complex Cryopreserved Tissue DNA Methylation Data Data Analyses Data Set Diagnosis Dissociation Drug Targeting Electrophysiology (science)Epigenetic Process Esthesia Evaluation Facial Pain Foundations Gene Expression Gene Expression Profiling Genes Genetic Databases Genetic Transcription Genomics Goals Head Headache Headache Disorders Health Helping to End Addiction Long-term Household Human Human Characteristics International Joints Knowledge Lead Length Maps Measurement Mediating Messenger RNA Methods Methyltransferase Migraine Modality Molecular Morphology Multiomic Data Neuroglia Neurons Nuclear RNA Pain Pain Clinics Patients Physiological Prevalence RNA Regulator Genes Regulatory Element Research Personnel Resolution Resources Sampling Spinal Spinal Ganglia Structure of trigeminal ganglion System Tissues Trigeminal System Uncertainty United States Universities Untranslated RNA Vertebral column allodynia cell type chronic pain chronic painful condition comparative effective therapy epigenome epigenomics gene regulatory network human RNA sequencing in vivo insight migraine treatment multidisciplinary multiple omics nervous system disorder neuronal cell body novel novel strategies response single-cell RNA sequencing somatosensory transcriptome transcriptome sequencing transcriptomics

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项目摘要

Migraine is a prevalent primary headache disorder that impacts one out of every four households in the United States. This complex neurologic disorder is mediated in part by alterations in trigeminal somatosensation, which manifests as head and facial pain and/or trigeminal allodynia. Despite its prevalence, there are currently limited effective treatments available for migraine, and our knowledge about human trigeminal system under baseline and migraine conditions are sparse. In response to RFA-NS-22-018, HEAL Initiative: Discovery and Functional Evaluation of Human Pain-associated Genes & Cells, we propose to form the Penn Human Precision Pain Center (Penn HPPC) to focus on elucidating molecular, cellular, epigenetic, and physiolog- ical profiles of human trigeminal ganglion (TG), which contains primary somatosensory neurons governing the head sensation, under baseline and migraine conditions. The Penn HPPC will be composed of Penn and inter- national investigators with multidisciplinary expertise. The PI, two co-PIs, and two co-Is are currently collaborat- ing on a single-soma deep RNA-seq of human dorsal root ganglion (DRG) neuron project, which form a strong foundation for this application. The Penn HPPC will contain three cores and perform three projects. Dr. Hao Wu, an expert in neuroepigenetics and single-cell genomics, will lead project 2 with support from Dr. Mingyao Li, the PI of the data core. This project aims to use two single-nucleus multi-omics assays, including the mas- sively parallel 10x Genomics multiome assay (3’ biased mRNA and open chromatin) and snmCAT-seq (full- length mRNA, open chromatin, and DNA methylation), to comprehensively map transcriptomic and epigenomic (chromatin accessibility and/or DNA methylation) profiles at single-nucleus resolution in control donors and those with migraine. In project 2, Aim 1 will focus on control trigeminal ganglion (TG) tissues, while Aim 2 will focus on TG tissues from "migraine" donors. The anticipated results will produce a comprehensive epigenetic and transcriptomic atlas to understand normal and abnormal trigeminal sensations associated with migraine. This rich resource may also lead to the discovery of new biomarkers for migraine diagnosis and novel potential drug targets for migraine treatment.

偏头痛是一种普遍的原发性头痛障碍，会影响每四个家庭中的一个美国。这种复杂的神经系统疾病部分是由三叉神经敏感的改变，部分介导的尽管率很高，但目前仍有有限的有效治疗可用于偏头痛，我们对人类三叉神经系统的了解基线和偏头痛条件很少。为了响应RFA-NS-22-018，Heal Initiative：Discovery和人类疼痛相关基因和细胞的功能评估，我们建议形成宾夕法尼亚人精密疼痛中心（Penn HPPC）专注于阐明分子，细胞，表观遗传和生理学人类三叉神经节（TG）的ICal剖面，其中包含主张的主要体感神经元头部感觉，基线和偏头痛条件。 Penn HPPC将由Penn和Inter- 具有多学科专业知识的国家调查员。 PI，两个Co-Pis和两个共同的合作 - 在人体背根神经节（DRG）神经元的单瘤深度RNA-seq上，它形成了强大的此应用程序的基础。 Penn HPPC将包含三个核心并执行三个项目。 Hao博士 Wu是神经毛皮物质和单细胞基因组学专家，将在Mingyao博士的支持下领导Project 2 Li，数据核的PI。该项目旨在使用两种单核多媒体测定法，包括Mas- 平行的10倍基因组学多组测定（3'偏见mRNA和开放染色质）和snmcat-seq（Full- 长度mRNA，开放的染色质和DNA甲基化），全面绘制转录组和表观基因组学（染色质的可及性和/或DNA甲基化）在对照供体中的单核分辨率下的曲线和/或与偏头痛。在项目2中，AIM 1将专注于控制三叉神经节（TG）组织，而AIM 2将集中在“偏头痛”供体的TG组织上。预期的结果将产生全面的表观遗传和转录组学图集以理解与偏头痛相关的正常和异常三叉神经感觉。这丰富的资源还可能导致发现新的生物标志物用于偏头痛诊断和新型潜在药物偏头痛治疗的靶标。