Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital, Medical Center, Cincinnati, OH, USA.
Division of Biomedical Informatics, Developmental Biology, and Pediatrics, Cincinnati, Children's Hospital Medical Center, Cincinnati, OH, USA.
Commun Biol. 2021 Sep 8;4(1):1049. doi: 10.1038/s42003-021-02562-8.
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.
肝母细胞瘤 (HB) 是儿童期最常见的原发性肝脏恶性肿瘤，目前对其分子机制的研究还很有限，而且对于耐药性疾病也缺乏有效的治疗选择。在 HB 的关键驱动细胞的研究中存在知识空白。在这里，我们通过对人类肿瘤、背景肝和患者来源的异种移植 (PDX) 进行单细胞核糖核酸测序 (scRNAseq) 分析，展示了肿瘤内的基因表达模式，并鉴定了肿瘤内细胞亚型异质性，根据儿童 HB 中的细胞内信号来定义不同的发病机制中的作用。我们已经通过遗传表达鉴定出 HB 中的驱动肿瘤细胞簇，可以对其进行检查以确定疾病机制和治疗方法。关键机制途径的鉴定以及独特的细胞群体为体外和体内发现和研究新的治疗策略提供了基础。
