By integration of single-cell RNA sequencing and the spatial transcriptome of liver samples, we provided a comprehensive spatial liver cell atlas of biliary atresia. In particular, we identified a cholangiocyte-enriched spatial niche with infiltration of activated hepatic stellate cells, activated portal fibroblasts, macrovascular endothelial cells and TREM2+ macrophages. These cells activate cholangiocyte through TNFSF12-TNFRSF12A pathway, leading to recruitment of monocytes via CCL2-CCR2 axis. This study reveals a cholangiocyte-enriched niche underscore a fibro-inflammatory ecosystem created by injured cholangiocytes and that TNFRSF12A is a therapeutic target for BA. [Link].
We identified a 14-gene prognostic signature at diagnosis that predicts two year, transplant-free survival in children with biliary atresia – the most common and leading indication for pediatric liver transplant. In addition, we found that the antioxidant N-acetly-cysteine (NAC) as a potential therauptic agent to prevent biliary injury and fibrosis. [Link].
We uncovered a shared connectome among the three main human cholangiopatheis (biliary atresia, primary biliary cholangitis and primary sclerosing cholangitis). [Link].
