Identification of distinct tumor cell populations and key genetic mechanisms through single cell sequencing in hepatoblastoma

通过肝母细胞瘤单细胞测序鉴定不同的肿瘤细胞群和关键遗传机制

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作者:Alexander Bondoc #, Kathryn Glaser #, Kang Jin #, Charissa Lake, Stefano Cairo, James Geller, Gregory Tiao, Bruce Aronow

Abstract

Hepatoblastoma (HB) is the most common primary liver malignancy of childhood, and molecular investigations are limited and effective treatment options for chemoresistant disease are lacking. There is a knowledge gap in the investigation of key driver cells of HB in tumor. Here we show single cell ribonucleic acid sequencing (scRNAseq) analysis of human tumor, background liver, and patient derived xenograft (PDX) to demonstrate gene expression patterns within tumor and to identify intratumor cell subtype heterogeneity to define differing roles in pathogenesis based on intracellular signaling in pediatric HB. We have identified a driver tumor cell cluster in HB by genetic expression which can be examined to define disease mechanism and treatments. Identification of both critical mechanistic pathways combined with unique cell populations provide the basis for discovery and investigation of novel treatment strategies in vitro and in vivo.

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