Supplementary file 3_Integrated microarray-based and single-cell transcriptomic analyses reveal cell adhesion-related fibrotic remodeling signatures in heart failure.docx

Key CARGs were identified using CytoHubba. Single-cell transcriptomic analysis was conducted to assess fibroblast states and gene dynamics. GSE36074 and a transverse aortic constriction (TAC) mouse model were used for validation by qPCR, Western blotting, and immunohistochemistry.</p>Results<p>Forty-five differentially expressed CARGs were identified and were mainly enriched in cell adhesion, extracellular region, and ECM-receptor interaction pathways.

The CelladhesionScore distinguished HF samples from controls, while the high-CelladhesionScore group showed enrichment of fibrosis-related pathways. Col5a1, Col6a1, and Fbn1 were identified as key CARGs. Single-cell analysis showed that these genes were predominantly expressed in fibroblasts and associated with fibroblast-state changes and ECM remodeling.

Their upregulation was consistently validated in external datasets and the TAC mouse model.</p>Conclusion<p>Col5a1, Col6a1, and Fbn1 are key CARGs associated with HF and fibroblast-mediated ECM remodeling. These findings provide new insights into cell adhesion-related molecular alterations in HF and may facilitate the identification of candidate biomarkers and therapeutic targets.</p>