DOI: 10.1002/ame2.12399
Single-cell transcriptomic sequencing identifies subcutaneous patient-derived xenograft recapitulated medulloblastoma
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
Abstract：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 the first to compare experimental models for MB at the single-cell level, providing valuable insights into model selection for different research purposes. sPDX and iPDX are suitable for drug testing and personalized therapy screenings, whereas GEMM models are valuable for investigating the interaction between tumor and TME cells.
Keywords：experimental modelsmedulloblastomasingle-cell sequencingsPDX
Publication Date：2025-03-30
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：15( 458-472 )