Mouse modeling of pediatric glioma, MYCN reveals intratumoral heterogeneity including neuronal and oligodendroglial lineage signatures (scRNA, set 1)

Pediatric glioma of the subclass MYCN are highly aggressive tumors frequently carrying MYCN amplifications, TP53 mutations, or both alterations. In order to understand the biology of these tumors better and to improve treatment options, we generated a genetically engineered model by breeding hGFAP-cre::TP53Fl/Fl::lsl-MYCN mice. All such mice developed aggressive forebrain tumors early in lifetime that mimic their human counterparts regarding histology, DNA methylation, and gene expression. A mouse model, hGFAP-cre::TP53Fl/Fl::lsl-MYCNFl/wt, for pediatric high-grade glioma, MYCN was generated. Tumors of three tumor-bearing mice were isolated and subsequently analyzed by droplet-based single-cell RNA-seq technology (10X Genomics).

MYCN亚型儿科神经胶质瘤是一类高侵袭性肿瘤，常伴随MYCN扩增、TP53突变，或二者兼具的基因改变。为深入解析这类肿瘤的生物学特性并优化治疗方案，我们通过繁育hGFAP-cre::TP53Fl/Fl::lsl-MYCN小鼠构建了基因工程模型。所有该类小鼠均在早年便形成侵袭性前脑肿瘤，在组织学、DNA甲基化与基因表达特征上均与人类对应肿瘤高度相似。本研究构建了针对MYCN亚型儿科高级别胶质瘤的小鼠模型hGFAP-cre::TP53Fl/Fl::lsl-MYCNFl/wt。我们分离了3只荷瘤小鼠的肿瘤组织，随后采用液滴法单细胞RNA测序（droplet-based single-cell RNA-seq）技术（10X Genomics平台）完成分析。