Project description:This study identified hepatic progenitor cell (HPC) niche-associated signalling pathways relevant in different chronic liver diseases using a high-throughput sequencing approach. The HPC niche was isolated using laser microdissection from patient samples diagnosed with hepatitis C virus (HCV) or primary sclerosing cholangitis (PSC), as models for hepatocellular or biliary regeneration. Differentially expressed genes in the HPC niche of PSC and HCV correlated to pathways involved in immune signalling, fibrogenesis and angiogenesis.
Project description:Cholangiocarcinomas (CCAs) are heterogeneous biliary cancers with dismal prognosis. Their etiologies remain mostly unclear, although primary sclerosing cholangitis (PSC) is a well-known risk factor. There is an urgent need of accurate non-invasive biomarkers for early CCA diagnosis and to predict patient´s prognosis, which may improve their clinical management and outcome. Here, by high-throughput proteomic analysis of serum extracellular vesicles (EVs), we identified diagnostic and/or prognostic biomarkers specific for CCAs in patients with PSC, and others common to all CCA subtypes. Bulk RNA tissue transcriptomic data revealed that these biomarkers are predominantly expressed in hepatobiliary tissues, being expressed in different liver cell types. Furthermore, single-cell RNAseq (scRNA-seq) analysis revealed that the expression of these biomarkers was preferentially found in malignant cholangiocytes within CCA tumors. In summary, these results highlight the potential of serum EVs to reflect cancer presence, especially for difficult-to-diagnose malignancies, including CCA."
Project description:Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are heterogeneous chronic autoimmune diseases that may share underlying pathogenic mechanisms. Herein, we compared simultaneously analyzed blood transcriptomes from patients with PBC, PSC, and IBD.
Project description:Primary sclerosing cholangitis (PSC) is a rare liver disease characterized by chronic inflammation and irreparable damage to the bile ducts. Due to a limited understanding of the underlying pathogenesis of disease, there remains a paucity of treatment options. As such, we sequenced healthy and diseased livers to compare the activity, interactions, and localization of immune and non-immune cells. This revealed that outside PSC scar regions, hepatocytes are transitioning to bile duct cells, whereas within the scars, there is an accumulation of immune cells. Of these cells, macrophages that typically contribute to tissue repair were enriched in immunoregulatory genes and were less responsive to stimulation. These cells are likely involved in maintaining hepatic inflammation and could be targeted in novel therapeutic development.
Project description:Primary sclerosing cholangitis (PSC) is a rare liver disease characterized by chronic inflammation and irreparable damage to the bile ducts. Due to a limited understanding of the underlying pathogenesis of disease, there remains a paucity of treatment options. As such, we sequenced healthy and diseased livers to compare the activity, interactions, and localization of immune and non-immune cells. This revealed that outside PSC scar regions, hepatocytes are transitioning to bile duct cells, whereas within the scars, there is an accumulation of immune cells. Of these cells, macrophages that typically contribute to tissue repair were enriched in immunoregulatory genes and were less responsive to stimulation. These cells are likely involved in maintaining hepatic inflammation and could be targeted in novel therapeutic development.
Project description:Primary sclerosing cholangitis (PSC) is a rare liver disease characterized by chronic inflammation and irreparable damage to the bile ducts. Due to a limited understanding of the underlying pathogenesis of disease, there remains a paucity of treatment options. As such, we sequenced healthy and diseased livers to compare the activity, interactions, and localization of immune and non-immune cells. This revealed that outside PSC scar regions, hepatocytes are transitioning to bile duct cells, whereas within the scars, there is an accumulation of immune cells. Of these cells, macrophages that typically contribute to tissue repair were enriched in immunoregulatory genes and were less responsive to stimulation. These cells are likely involved in maintaining hepatic inflammation and could be targeted in novel therapeutic development.
Project description:Primary sclerosing cholangitis (PSC) is a rare liver disease characterized by chronic inflammation and irreparable damage to the bile ducts. Due to a limited understanding of the underlying pathogenesis of disease, there remains a paucity of treatment options. As such, we sequenced healthy and diseased livers to compare the activity, interactions, and localization of immune and non-immune cells. This revealed that outside PSC scar regions, hepatocytes are transitioning to bile duct cells, whereas within the scars, there is an accumulation of immune cells. Of these cells, macrophages that typically contribute to tissue repair were enriched in immunoregulatory genes and were less responsive to stimulation. These cells are likely involved in maintaining hepatic inflammation and could be targeted in novel therapeutic development.
Project description:Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation and progressive fibrosis of the biliary tree. The bile acid receptor TGR5 is found on biliary epithelial cells (BECs), where it promotes secretion, proliferation and tight junction integrity. Thus, we speculated that changes in TGR5 expression in BECs may contribute to PSC pathogenesis.
