Focal Adhesion Genes and Proteins Are Differentially Expressed Across Cell Types in Down Syndrome

Down syndrome (DS), caused by an extra copy of chromosome 21, leads to widespread gene expression changes through mechanisms such as transcriptional dysregulation and altered protein interactions. These disruptions contribute to a range of clinical features, including impaired wound healing, immune dysfunction, and neurodevelopmental abnormalities. This study focused on how DS affects fibroblast morphology and motility—processes critical for tissue repair and brain development. Using quantitative immunocytochemistry and image analysis, we found that DS fibroblasts displayed a broader, less polarized shape, with increased cell perimeter and reduced aspect ratio. However, levels of key adhesion proteins like vinculin, FAK, and β-actin were not significantly different from controls. To investigate upstream causes, we performed a meta-analysis of RNA sequencing datasets across multiple DS models. While results for focal adhesion genes were variable, we observed consistent upregulation of ECM components such as laminins and integrins. These findings suggest that altered fibroblast morphology in DS may stem from changes in ECM composition and adhesion signaling rather than core protein abundance. Such changes may impair cell polarization and mechanosensing, contributing to clinical symptoms. Because similar mechanisms regulate neuronal migration, these disruptions could also affect brain development. Future studies should integrate transcriptomics with spatial and functional analyses to fully understand DS cellular pathology.