PDF(Pubmed)
Abstract：
Neuroblastoma is a childhood developmental cancer; however, its embryonic origins remain poorly understood. Moreover, in-depth studies of early tumor-driving events are limited because of the lack of appropriate models. Herein, we analyzed RNA sequencing data obtained from human neuroblastoma samples and found that loss of expression of trunk neural crest-enriched gene MOXD1 associates with advanced disease and worse outcome. Further, by using single-cell RNA sequencing data of human neuroblastoma cells and fetal adrenal glands and creating in vivo models of zebrafish, chick, and mouse, we show that MOXD1 is a determinate of tumor development. In addition, we found that MOXD1 expression is highly conserved and restricted to mesenchymal neuroblastoma cells and Schwann cell precursors during healthy development. Our findings identify MOXD1 as a lineage-restricted tumor-suppressor gene in neuroblastoma, potentiating further stratification of these tumors and development of novel therapeutic interventions.
摘要：
神经母细胞瘤是一种儿童发育性癌症；然而，它的胚胎起源仍然知之甚少。此外，由于缺乏合适的模型，对早期肿瘤驱动事件的深入研究受到限制。在这里，我们分析了从人类神经母细胞瘤样本获得的RNA测序数据,发现躯干神经嵴富集基因MOXD1的表达缺失与疾病进展和预后恶化相关.Further,通过使用人类神经母细胞瘤细胞和胎儿肾上腺的单细胞RNA测序数据，并创建斑马鱼的体内模型，小鸡,和老鼠,我们表明MOXD1是肿瘤发展的决定因素。此外,我们发现MOXD1的表达是高度保守的，并且在健康发育过程中仅限于间质神经母细胞瘤细胞和雪旺氏细胞前体。我们的发现将MOXD1确定为神经母细胞瘤中的谱系限制性肿瘤抑制基因，加强这些肿瘤的进一步分层和新型治疗干预措施的发展。
