Transcriptome dynamics during vocal fold injury and repair

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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.