Yin Lab

  • Hepatic Stellate Cells

    Hepatic stellate cells are liver-specific mesenchymal cells that play vital roles in liver physiology.  In healthy liver, hepatic stellate cells are kept quiescent and contain numerous vitamin A lipid droplets, constituting the largest reservoir of vitamin A in the body.  When the liver is injured due to viral infection or hepatic toxins, hepatic stellate cells transform into activated myofibroblast-like cells to generate scar tissue.  In chronic liver disease, prolonged and repeated activation of hepatic stellate cells causes liver fibrosis as characterized by widespread scar formation and perturbation of liver architecture and function.  Cirrhosis, the end stage of fibrosis, is among the leading causes of death worldwide with no cure except for liver transplant.  

    We developed the first zebrafish reporter line of hepatic stellate cells and showed that the zebrafish hepatic stellate cells share many similarities with their mammalian counterparts, including morphology, location, lipid storage, gene expression profile, and responses to liver injury. 

    Currently, we are using the power of imaging and genetics in zebrafish to investigate the contribution of hepatic stellate cells to liver development and regeneration. We also study the molecular mechanisms underlying their activation in liver injures induced by alcohol and other hepatic toxins.  Finally, we are conducting high throughput chemical screens to identify drugs that influence the development and activation of hepatic stellate cells.

 
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    In healthy liver, hepatic stellate cells are kept quiescent and their main function is to store vitamin A droplets. When the liver is injured, hepatic stellate cells transform into activated myofibroblast-like cells to generate scar tissue. (adopted from Iredale, 2007. The Journal of Clinical Investigation 117(3): 539-548).

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    Tg(hand2:EGFP) expression marks hepatic stellate cells in zebrafish. This picture shows a confocal scanning image of the liver in adult zebrafish that are labeled by Tg(hand2:EGFP) (green) and Phalloidin (red)
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    Acute ethanol treatment on zebrafish larvae triggers activation of hepatic stellate cells and deposition of extracellular matrix proteins.  (A and B) Confocal single-plane images of hepatic stellate cells in untreated controls (A) and larvae treated with 2% ethanol from 96 to 120 hpf (B).  (A’ and B’) same views as (A and B), but showing the deposition of laminin. Hepatic stellate cells in ethanol-treated animals up-regulated their production of laminin and exhibited changes in morphology. (C and D) Confocal projections showing hepatic stellate cells in untreated controls and ethanol-treated larvae at 3 days post-treatment (dpt). Hepatic stellate cells in ethanol-treated larvae are more numerous and show more elongated cell bodies and less-complex cytoplasmic processes.