Human Embryonic Stem Cell–Derived Hepatoblasts Are an Optimal Lineage Stage for Hepatitis C Virus Infection

 

Fang Yan, et al., 2017, hep.29134

 

 

Speaker: Shun-Yun Hou(侯舜芸)

Commentator: Dr. Kung-Chia Young(楊孔嘉老師)

Time: 14:00~15:00, Nov.22, 2017

Place: Room 601

 

 

Abstract:

Hepatocellular carcinoma (HCC) is the second lethal cancer in the worldwide. It occurs in chronic liver inflammation, and mostly related to chronic viral hepatitis infection (hepatitis B or C). There are approximately 25% cases caused by hepatitis C virus (HCV), available drugs used in HCC treatment are not only expensive but cause many side effect in patients. Previous study, shows that HCV is a specific infection in the liver but only 7-20% hepatocytes were infected [1]. Maturation of hepatic cells acquisition is achieved through multiple stages of hepatic lineage specification, however, hepatitis C virus (HCV) infection is maturationally lineage-dependent remains unclear. A well established process of hepatic differentiation, from human embryonic stem cells (hESCs) to definitive endodermal stem cells (hDECs), hepatic stem cells (hHpSCs), hepatoblasts (hHBs), and finally to hepatocytes (hHeps) was used as a guide for better understanding HCV infection of preferred linage that could possibly help in mounting and infection[2]. In this study, it was shown that hHBs were more susceptible lineage stage to HCV infection. The author observed translocation of occludin (HCV receptor) or upregulation of HCV replication gene (e.g.CRLF3, ITGA7) which is a reason why HCV prefer to infect the hHBs. HCV-infected hHBs transplanted to rescue liver damage of Fah–/–Rag2–/–mice, the hHBs lineage were maintained in this stage over 12 weeks during HCV core protein persistence. Interferon β(IFN-β) was an important innate immune factor in hHBs when HCV infected. The author used siRNA to suppress IFN-β and enhance HCV infection in F/R mice. This study demonstrated that hESCs–derived hHBs are the optimal lineage stage for HCV infectivity. Engrafted HCV-hHBs of F/R mice model enable us to understand the dynamic of HCV infection, symptoms and a possible anti-HCV treatment.

References

1. Liang, Y., et al., Visualizing hepatitis C virus infections in human liver by two-photon microscopy. Gastroenterology, 2009. 137(4): p. 1448-58.

2. Qin, J., et al., Connexin 32-mediated cell-cell communication is essential for hepatic differentiation from human embryonic stem cells. Sci Rep, 2016. 6: p. 37388.