A Developmentally Prometastatic Niche in Neonatal Liver to Hepatoblastoma mediated by Cxcl1/Cxcr2 Axis

Hepatoblastoma (HB) is the most common pediatric liver cancer. Its exclusive occurrence in very young children leads us to investigating whether the immature liver provides a protumorigenic niche to HB development. We employed the single-cell RNA-sequencing (sc-RNAseq) to comprehensively profile the HB tumors and their microenvironment in the orthotopic transplantation models established in postnatal day 5 and 60. We demonstrated that the neonatal liver provides a prometastatic niche to HB development via Cxcl1/Cxcr2 axis-mediated HB-aHSC interaction. We first established the orthotopic transplantation models of hepatoblastoma in postnatal day 5 and 60 mice (P5Tx and P60Tx models). Then we performed single-cell RNA-sequencing (sc-RNAseq) using tumor and liver tissues from both models. The top candidate cell type and gene identified by sc-RNAseq are investigated for their roles in HB cell growth, migration, and survival.