Re-Analysis of GSE119606 Hepatic Stellate Cells Treated with TGF-beta

Abstract

The original study addressed the progression of chronic liver disease to fibrosis, emphasizing how transforming growth factor activates hepatic stellate cells to produce extracellular matrix and how epigenetic regulators such as EZH2 amplify this fibrogenic response. We reanalyzed the GSE119606 RNAseq data to better characterize the TGFinduced stellatecell signature using a standardized bioinformatics pipeline. The workflow began by retrieving raw counts and metadata from ARCHS4, structuring them in AnnData objects, and applying differential expression analysis with limmavoom to generate a gene signature. This signature was then examined with enrichment tools to identify overrepresented biological processes, pathways, transcription factor motifs, and phenotypic associations, and with a perturbationmatching tool to find smallmolecule and gene perturbations that either mimic or reverse the observed expression pattern. The reanalysis confirmed that the upregulated signature is dominated by carbohydrate and glycoconjugate synthesis pathways and extracellularmatrix remodeling, while the downregulated signature suppresses monosaccharide biosynthesis and immuneresponse transcription factors. Perturbation matching highlighted compounds that recapitulate the TGF signature and identified potential therapeutic agents capable of reversing it, underscoring druggable nodes in stellatecell activation and liver fibrosis.