Modeling Hepatoblastoma: Identification of Distinct Tumor Cell Populations and Key Genetic Mechanisms through Single Cell Sequencing (bulk)

Hepatoblastoma (HB) is the most common primary liver malignancy of childhood. However, molecular investigations of the disease are limited and effective treatment options are lacking. The use of patient derived xenografts (PDX) to study biology and treatment strategies of HB has proven to be a useful tool. There is currently a knowledge gap in the investigation of key driver cells of HB in PDX models. Key driving pathways of HB tumor including WNT, AP-1, Hedgehog, Notch and MAPK pathways and genes such as GPC3, DLK1 and HMGA2 have been identified in primary HB tumor and PDX as integral players in HB tumor growth. Cell clusters have been defined with distinct roles in tumor development. Cell populations with initiating, angiogenic (endothelial), maintenance, and progression signatures have been identified in one HB patient tumor and corresponding PDX tumor. Critical pathways combined with identification of distinct cell populations within HB tumor will allow for investigation of novel treatment strategies in vitro and in vivo. Overall design: Hepatoblastoma tumor was implanted into NSG mice and surgically separated into new mice to generate sequential passages of tumor (F). PDX tumor was compared to parent tumor as well as backgorund liver to characterize maintenance of tumor phenotype over time. Two background liver, two patient HB tumor samples and six PDX passages per patient tumor (12 total). Six additional PDX samples were examined to see response to chemo treatment: three control and three treated with irinotecan.