Genetic lineage tracing analysis of the cell of origin of hepatotoxin-induced liver tumors in mice

摘要: The expression of biliary/progenitor markers by hepatocellular carcinoma (HCC) is often associated with poor prognosis and stem cell-like behaviors tumor cells. Hepatocellular adenomas (HCAs) also express frequently act as precursor lesions for HCC. However, the cell origin HCA HCC that expresses these remains unclear. Therefore, to evaluate if mature hepatocytes give rise tumors understand molecular pathways involved in tumorigenesis, we lineage-labeled injecting adeno-associated virus containing thyroxine-binding globulin promoter-driven causes recombination (AAV-TBG-Cre) into RosaYFP mice. Yellow fluorescent protein (YFP) was present >96% before exposure carcinogens. We treated AAV-TBG-Cre; mice diethylnitrosamine (DEN), followed multiple injections carbon tetrachloride induce carcinogenesis fibrosis found nodules were YFP+ lineage-labeled; positive osteopontin, SRY (sex determining region Y)-box 9, epithelial adhesion molecule; enriched transcripts such prominin 1, Cd44, delta-like 1 homolog. Next, performed converse experiment forkhead box L1(Foxl1)-positive hepatic progenitor cells simultaneously None expressed YFP, indicating Foxl1-expressing are not hepatotoxin-induced liver tumors. confirmed derived from Foxl1-Cre-marked a second model toxin-induced neoplasia, using DEN 3,3′,5,5′-tetrachloro-1,4-bis(pyridyloxy)benzene (TCPOBOP). Conclusion: Hepatocytes DEN/carbon DEN/TCPOBOP induced (Hepatology 2016;64:1163-1177)