Single‐cell transcriptomic sequencing identifies subcutaneous patient‐derived xenograft recapitulated medulloblastoma

作者：Jiayu Gao, Yahui Zhao, Ziwei Wang, Fei Liu, Xuan Chen, Jialin Mo, Yifei Jiang, Yongqiang Liu, Peiyi Tian, Yanong Li, Kaiwen Deng, Xueling Qi, Dongming Han, Zijia Liu, Zhengtao Yang, Yixi Chen, Yujie Tang, Chunde Li, Hailong Liu, Jiankang Li, Tao Jiang · 发表于：Animal Models and Experimental Medicine · 年份：2024 · DOI：10.1002/ame2.12399 · 被引用次数：4 · 研究领域：Single-cell and spatial transcriptomics、Glioma Diagnosis and Treatment、Cancer Genomics and Diagnostics

BACKGROUND: Medulloblastoma (MB) is one of the most common malignant brain tumors that mainly affect children. Various approaches have been used to model MB to facilitate investigating tumorigenesis. This study aims to compare the recapitulation of MB between subcutaneous patient-derived xenograft (sPDX), intracranial patient-derived xenograft (iPDX), and genetically engineered mouse models (GEMM) at the single-cell level. METHODS: We obtained primary human sonic hedgehog (SHH) and group 3 (G3) MB samples from six patients. For each patient specimen, we developed two sPDX and iPDX models, respectively. Three Patch+/- GEMM models were also included for sequencing. Single-cell RNA sequencing was performed to compare gene expression profiles, cellular composition, and functional pathway enrichment. Bulk RNA-seq deconvolution was performed to compare cellular composition across models and human samples. RESULTS: Our results showed that the sPDX tumor model demonstrated the highest correlation to the overall transcriptomic profiles of primary human tumors at the single-cell level within the SHH and G3 subgroups, followed by the GEMM model and iPDX. The GEMM tumor model was able to recapitulate all subpopulations of tumor microenvironment (TME) cells that can be clustered in human SHH tumors, including a higher proportion of tumor-associated astrocytes and immune cells, and an additional cluster of vascular endothelia when compared to human SHH tumors. CONCLUSIONS: This study was t...