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Characterization of human DRG at the single cell level via integrated transcriptomics and spatial proteomics

通过整合转录组学和空间蛋白质组学在单细胞水平表征人类 DRG

基本信息

批准号：
10593846
负责人：
Valeria Cavalli
金额：
$ 64.01万
依托单位：
WASHINGTON UNIVERSITY
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：
2022-09-30 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10593846
关键词：
ATAC-seq Acute Pain Adult Affect Afferent Neurons American Antibodies Architecture Atlases Bioinformatics Biological Markers Biological Models Blood Vessels Cell Communication Cell Nucleus Cell physiology Cells Chromatin Classification Communicable Diseases Consent Cytometry Data Data Analyses Data Set Detection Development Diabetes Mellitus Diabetic Neuropathies Disease Progression Environment Future Gene Expression Gene Expression Profile Gene Expression Profiling Genes Genetic Transcription Genomics Goals Human Image Immune Immunology Infectious Diseases Research Malignant Neoplasms Maps Measurement Measures Messenger RNA Methods Molecular Molecular Profiling Natural regeneration Neuroglia Neurons Nociceptors Operative Surgical Procedures Organ Organ Donor Pain Pain Research Pathologic Pathway Analysis Pathway interactions Peripheral Peripheral Nervous System Diseases Population Positioning Attribute Preparation Process Proteins Proteomics Quality Control Recording of previous events Research Resolution Rodent Rodent Model Role Sampling Sensory Signal Transduction Small Nuclear RNA Spinal Ganglia Taxonomy Technology Testing Tissue Donations Tissue-Specific Gene Expression Tissues Translational Research Translations Treatment outcome Validation base cancer therapy cell type chronic pain chronic painful condition computational pipelines design disease prognosis ganglion cell human tissue improved insight inter-individual variation knowledge translation nerve injury neuronal cell body novel therapeutics opioid overuse pain perception peripheral pain pre-clinical protein biomarkers protein expression response single cell sequencing spatial relationship tool transcriptome transcriptome sequencing transcriptomics transmission process

项目摘要

Project Abstract – Project 2 Rodent models of dorsal root ganglia (DRG) have been extremely useful in identifying the cellular and molecular mechanisms involved in pain, nerve injury, regeneration, degeneration, and various forms of peripheral neuropathies. However, translation of preclinical findings may be greatly improved by validation in human tissues. Since differences exist between rodent and human sensory neurons, a detailed study of all cells within human DRG is critical for future treatment of painful state, nerve injuries as well as peripheral neuropathies. The difficulty to gain access to human DRG has hampered progress on that front. Our collaborative team is uniquely positioned to tackle this problem. We have gained expertise in the surgical procedure for extraction of human DRG from organ donors consenting to tissue donation for research and the preparation of viable adult DRG cells for functional and molecular studies. Combined with our strong expertise in single cell sequencing, imaging mass cytometry and bioinformatics approaches, we will define at the single cell level the molecular profile of neuronal and non-neuronal cells within human DRG tissue. We will integrate gene expression profile with imaging mass cytometry (IMC), a tissue-based proteomic analysis that allows the detection of over 30 protein markers simultaneously on tissue sections at the single-cell level while retaining the spatial relationships of the cells. IMC enables a variety of distinct cell types to be analyzed concurrently at a single-cell resolution and is reshaping the ability to interrogate both the intercellular interactions and the architectural relationships between cells and their native microenvironment. This spatially-resolved multiplexed profiling approach has been applied to cancer, diabetes, immunology, and infectious disease research, identifying functionally distinct immune cell subpopulations associated with disease progression, treatment outcomes, and biomarkers for disease prognosis. We will develop computational approaches for integrated IMC and single cell transcriptomic analysis of hDRG. Application of this spatially-resolved, highly multiplexed, single-cell transcriptomics and proteomic profiling approach to pain research will likely reshape our ability to interrogate cell population and gene expression changes and their spatial relationships between neurons and non-neuronal cells in healthy and painful conditions. By integrating the cellular, spatial and functional branches of the human DRG atlas we will dramatically expand the characterization of human DRG in healthy and painful states. This project will generate a reference atlas for human DRG and define inter-individual variability of healthy human DRG tissue and DRG from painful conditions with single cell resolution.

项目摘要-项目2