Single-cell analysis of hepatoblastoma identifies distinct tumor cell signatures that predict susceptibility to chemotherapy using patient-specific tumor spheroids

Method: In this study we use single cell RNA sequencing (scRNA-seq) to distinguish HB tumor cells from non-tumor cells and to identify distinct tumor cell types that account for the heterogeneity of HB. We also use a novel method to grow HB tumor cells as patient-specific spheroids (PDS) and show how this can be used to predict treatment response and identify novel therapeutic targets. Results: This study establishes that tumor heterogeneity can be defined by the relative proportions of five distinct subtypes of tumor cells. Notably, patient-derived HB spheroid cultures predict differential responses to treatment based on the transcriptomic signature of each tumor, suggesting a path forward for precision oncology for these tumors. Conclusions: These results define HB tumor heterogeneity with single-cell resolution and demonstrate that patient-derived spheroids can be used to evaluate responses to chemotherapy. Overall design: Single-cell RNA sequencing based on Seq-Well S^3 protocol of nine hepatoblastoma patients tumor tissues with matched normal samples and spheroid samples grown from the tumor tissues.