Chronic bile duct disease can cause liver scarring and, in some cases, result in the need for liver transplantation. The scarring process can be damaging to the liver, but the cells involved in scarring also play a role in healing and regenerating the liver.
Activated hepatic stellate cells orchestrate scarring during liver injury. Here we define morphologically and transcriptionally discreet subpopulations of aHSCs.
Using human tissue, bile duct organoids and animal models of biliary disease, we show that non-canonical Wnt signalling is important in initiating biliary scarring.
This work identifies the loss of stem cell adhesion to Fibronectin in the niche ECM as a previously unknown aging mechanism
These results demonstrate that enhanced WNT signaling is a characteristic of CC and suggest that targeting WNT signaling pathways has potential as a therapeutic strategy for Cholangiocarcinoma.
This work shows age-related intrinsic properties that functionally distinguish satellite cells and suggest a promising therapeutic avenue for the treatment of muscle-wasting diseases.