Transcriptome dynamics during vocal fold injury and repair

声带损伤和修复过程中的转录组动态

基本信息

批准号：
10679705
负责人：
Kristy DeRhea Wendt
金额：
$ 4.33万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
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：
2023-02-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10679705
关键词：
Adult Affect Bioinformatics Cell Communication Cell Lineage Cells Chromosome Mapping Cicatrix Communication Complex Control Animal Data Development Disease Dysphonia Engineering Environment Epithelial Cells Epithelium Extracellular Matrix FVB/N Mouse Fibroblasts Fibrosis Gene Expression Gene Expression Profiling Genes Goals Health Health Care Costs Heterogeneity Immune Individual Inflammatory Inflammatory Response Injury Laboratories Lamina Propria Larynx Libraries Location Macrophage Maps Mentors Mesenchyme Modeling Molecular Movement Mucous Membrane Multiple Wounds Mus Myofibroblast Natural regeneration Occupational Operative Surgical Procedures Organ Outcome Patients Phase Phenotype Pliability Population Population Heterogeneity Positioning Attribute Process Quality of life Research Research Training Role Spatial Distribution Suspensions Testing Therapeutic Time Tissue Engineering Tissue Harvesting Tissues Translations Unemployment Voice Work biomarker identification cell type differential expression engineering design experimental study healing in vivo injury and repair innovation innovative technologies mouse model novel marker regenerative approach repaired response response to injury single-cell RNA sequencing therapeutic target tissue regeneration tissue repair transcriptome transcriptome sequencing vocal cord wound wound healing

项目摘要

ABSTRACT Vocal fold (VF) scarring is the single greatest cause of poor voice after vocal fold surgery and can have a significant negative impact on quality of life. VF scarring is characterized by disorganization in the extracellular matrix (ECM) of the lamina propria as well as alterations in the integrity of the surrounding epithelium and an overall reduction in VF pliability. There is no treatment that can eliminate formed scars or reverse scar formation. Research specific to vocal fold scarring has been limited by a lack of understanding of the contributing subpopulations of cells and cell state dynamism in the context of injury space. The overall goal of this work is to eluicate subpopulations, location, and proximity of cells that contribute to the VF injury response and repair in vivo. Aim 1 will use single cell RNA sequencing analysis to identify the subpopulations of cells present during injury and healing, as well as genes that are differentially expressed (DE) between and among them to determine where cell-specific changes in the transcriptome are important. Aim 2 will investigate spatial differential expression using spatial RNA sequencing analysis to identify niches enriched for distinct gene sets and localize cell subpopulations to the VF in space and time during wound healing and repair. The central hypothesis of this mentored research training proposal is that there are subpopulations of cells – immune, fibroblasts and epithelial cells that respond to injury, and that these cells’ spatial location and proximity to each other have a significant effect on coordinated gene expression. This proposal will identify participating cell subpopulations and map gene expression positional identities to niches in the VF during inflammatory, proliferative, remodeling and mature scar phases of wound healing to inform targeted regenerative approaches.

抽象的声带 (VF) 疤痕是声带手术后声音不佳的最大原因，并且可能会导致声带疤痕。 VF 疤痕的特点是细胞外组织紊乱。固有层基质（ECM）以及周围上皮完整性和 VF 柔韧性整体降低没有任何治疗方法可以消除已形成的疤痕或逆转疤痕。由于缺乏对声带疤痕形成的了解，专门针对声带疤痕的研究受到限制。在损伤空间的背景下贡献细胞亚群和细胞状态动态。这项工作是为了阐明导致心室颤动损伤反应的细胞亚群、位置和接近程度目标 1 将使用单细胞 RNA 测序分析来识别细胞亚群。损伤和愈合过程中存在的基因，以及之间差异表达（DE）的基因目标 2 将在空间上研究转录组中哪些细胞特异性变化是重要的。使用空间 RNA 测序分析差异表达来识别富含不同基因集的生态位并在伤口愈合和修复过程中将细胞亚群在空间和时间上定位到 VF。这个指导性研究培训计划的假设是存在细胞亚群——免疫、对损伤做出反应的成纤维细胞和上皮细胞，以及这些细胞的空间位置和彼此的接近程度其他对协调基因表达有显着影响该提案将识别参与细胞。亚群并将基因表达位置特征映射到炎症期间 VF 中的生态位，伤口愈合的增殖、重塑和成熟疤痕阶段，为目标再生提供信息接近。