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| Item Type: | Article |
|---|---|
| Title: | Liver transcriptome analysis reveals PSC-attributed gene set associated with fibrosis progression |
| Creators Name: | Laschtowitz, A., Lindberg, E.L., Liebhoff, A.M., Liebig, L.A., Casar, C., Steinmann, S., Guillot, A., Xu, J., Schwinge, D., Trauner, M., Lohse, A.W., Bonn, S., Hübner, N. and Schramm, C. |
| Abstract: | BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is a chronic heterogenous cholangiopathy with unknown etiology where chronic inflammation of the bile ducts leads to multifocal biliary strictures and biliary fibrosis with consecutive cirrhosis development. We here aimed to identify a PSC-specific gene signature associated with biliary fibrosis development. METHODS: We performed RNA-sequencing of 47 liver biopsies from people with PSC (n = 16), primary biliary cholangitis (PBC, n = 15), and metabolic dysfunction-associated steatotic liver disease (MASLD, n = 16) with different fibrosis stages to identify a PSCspecific gene signature associated with biliary fibrosis progression. For validation, we compared an external transcriptome data set of liver biopsies from people with PSC (n = 73) with different fibrosis stages (baseline samples from NCT01672853). RESULTS: Differential gene expression analysis of the liver transcriptome from patients with PSC with advanced vs. early fibrosis revealed 431 genes associated with fibrosis development. Of those, 367 were identified as PSC-associated when compared with PBCorMASLD.Validation against an external data set of 73 liver biopsies from patients with PSC with different fibrosis stages led to a condensed set of 150 (out of 367) differentially expressed genes. Cell type specificity assignment of those genes by using published single-cell RNA-Seq data revealed genetic disease drivers expressed by cholangiocytes (e.g. CXCL1, SPP1), fibroblasts, innate, and adaptive immune cells while deconvolution along fibrosis progression of the PSC, PBC, and MASLD samples highlighted an early involvement of macrophage- and neutrophil-associated genes in PSC fibrosis. CONCLUSIONS: We reveal a PSC-attributed gene signature associated with biliary fibrosis development that may enable the identification of potential new biomarkers and therapeutic targets in PSC-related fibrogenesis. |
| Keywords: | Primary Sclerosing Cholangitis, Biliary Fibrosis, Bulk RNA-Sequencing, Liver Transcriptome |
| Source: | JHEP Reports |
| ISSN: | 2589-5559 |
| Publisher: | Elsevier |
| Volume: | 7 |
| Number: | 3 |
| Page Range: | 101267 |
| Number of Pages: | 1 |
| Date: | March 2025 |
| Official Publication: | https://doi.org/10.1016/j.jhepr.2024.101267 |
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