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 

机构地区：[1]BGI-Shenzhen,Shenzhen,China [2]Yidu Central Hospital of Weifang,Weifang,China [3]Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University,Beijing,China [4]Beijing Neurosurgical Institute,Capital Medical University,Beijing,China [5]China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital,Capital Medical University,Beijing,China [6]BGI-Wuhan,Wuhan,China [7]Department of Radiotherapy,Beijing Tiantan Hospital,Capital Medical University,Beijing,China [8]College of Life Sciences,University of Chinese Academy of Sciences,Beijing,China [9]Department of Pathophysiology,Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education,Shanghai Jiao Tong University School of Medicine,Shanghai,China [10]University of Michigan-Shanghai Jiao Tong University Joint Institute,Shanghai Jiao Tong University,Shanghai,China [11]Department of Biomedical Engineering,University of Michigan,Ann Arbor,Michigan,USA [12]Research Center of Chinese Herbal Resources Science and Engineering,School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou,China [13]Department of NeuroPathology,Sanbo Brain Hospital,Capital Medical University,Beijing,China [14]Chinese Institute for Medical Research,Beijing,China

出　　处：《Animal Models and Experimental Medicine》2025年第3期458-472,共15页动物模型与实验医学(英文)

基　　金：National Key Research and Development Program of China,Grant/Award Number:2022ZD0210100;Beijing Nova Star Program,Grant/Award Number:2022002;Natural Science Foundation of Beijing and Haidian Collaboration Foundation,Grant/Award Number:L232079;National Natural Science Foundation of China,Grant/Award Number:82172608,82273343,81902975 and 82101356;Capital Medical University Fund for Excellent Young Scholars,Grant/Award Number:KCB2304。

摘　　要：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 value 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.

关 键 词：experimental models MEDULLOBLASTOMA single-cell sequencing sPDX 

分 类 号：R73[医药卫生—肿瘤]