Date of Graduation

5-2024

Document Type

Thesis

Degree Name

Bachelor of Science in Biomedical Engineering

Degree Level

Undergraduate

Department

Biomedical Engineering

Advisor/Mentor

Wolchok, Jeffrey C.

Committee Member

Song, Younghye

Abstract

Volumetric Muscle Loss (VML) injuries are known to disrupt the normal regenerative process via fibrosis leading to an extensive permanent loss of muscle function. The specific causation of this disruption remains to be defined; however, with new developments in transcriptomics, genetic trends can be identified across regions of tissue over time. This study follows VML injuries within the tibialis anterior of a mouse model for fifteen days after initial injury to attempt to identify expected transitions in healing. Genetic presence began to become more diversified as recovery progressed from four to fifteen days post injury with spatial clusters becoming globalized based on inflammatory or regenerative effects. The evolution of these clusters was based upon the elimination of inflammatory related genes and appearance of muscle diversification related genes as fifteen days post injury was approached. Limitations did exist regarding the heterogeneity of spatial counts and distribution; however, improvements in procedure and study design would likely mitigate this in future studies. Extensive percentages of mitochondrial gene counts were established at regions of low spatial counts and needs to be investigated further to ensure that future studies involving possible cellular death will not affect spatial counts. Low resolution and specificity of spatial clusters also limited the ability to draw extensive conclusions regarding transitions in healing, but integrating this technology with single-cell transcriptomics, immunofluorescence, and other quantitative assays will greatly improve these issues. Overall, spatial transcriptomics offers researchers an innovative approach to quantify and visualize stages of healing in VML recovery studies that could be leveraged in conjunction with existing methods to better understand the complex cytokine pathways behind these injuries.

Keywords

Volumetric Muscle Loss; Spatial Transcriptomics; Transcriptomics; Bioinformatics; RNA Sequencing; Histology

Available for download on Wednesday, April 23, 2025

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