Project description:Comparison of transcripts between human hepatocytes, human hepatocytes reprogrammed into biliary cells, and human biliary cells shows similarities between reprogrammed cells and the untreated biliary population
Project description:Biliary diseases can cause inflammation, fibrosis, bile duct destruction and eventually liver failure. There are no curative treatments for biliary disease except for liver transplantation. New therapies are urgently required. We have purified human Biliary Epithelial Cells (hBEC) from discarded human livers. hBECs were tested as a cell therapy in a mouse model of biliary disease where the conditional deletion of Mdm2 in cholangiocytes causes senescence, biliary strictures and fibrosis. hBEC are expandable, phenotypically stable and help restore biliary structure and function, highlighting their regenerative capacity and a potential alternative to liver transplantation for biliary disease.
2022-03-03 | GSE155498 | GEO
Project description:Gut microbiota of biliary atresia
| PRJNA492189 | ENA
Project description:biliary microbiota of multiple choledocholithiasis
| PRJNA1121231 | ENA
Project description:gut microbiota in biliary atresia
Project description:Normothermic machine perfusion (NMP) after static cold storage is increasingly used for preservation and assessment of human donor livers prior to transplantation. Biliary viability assessment during NMP reduces the risk of post-transplant biliary complications. However, understanding molecular changes in the biliary system during NMP remains incomplete. Here, we performed RNA-seq analysis of donor livers undergoing NMP treatment and compared livers with biliary viability scores that were acceptable for transplantation vs those that were not.
Project description:Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR.