DOI: 10.1002/ame2.12399
Single-cell transcriptomic sequencing identifies subcutaneous patient-derived xenograft recapitulated medulloblastoma
Jiayu Gao1
Yahui Zhao2
Ziwei Wang3
Fei Liu4
Xuan Chen5
Jialin Mo6
Yifei Jiang7
Yongqiang Liu8
Peiyi Tian5
Yanong Li9
Kaiwen Deng4
Xueling Qi10
Dongming Han5
Zijia Liu5
Zhengtao Yang5
Yixi Chen11
Yujie Tang6
Chunde Li2
Hailong Liu12
Jiankang Li13
Tao Jiang2
1.BGI-Shenzhen,Shenzhen,China;Yidu Central Hospital of Weifang,Weifang,China2.Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University,Beijing,China;Beijing Neurosurgical Institute,Capital Medical University,Beijing,China;China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital,Capital Medical University,Beijing,China3.BGI-Shenzhen,Shenzhen,China;BGI-Wuhan,Wuhan,China4.Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University,Beijing,China;Department of Radiotherapy,Beijing Tiantan Hospital,Capital Medical University,Beijing,China5.BGI-Shenzhen,Shenzhen,China;College of Life Sciences,University of Chinese Academy of Sciences,Beijing,China6.Department of Pathophysiology,Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education,Shanghai Jiao Tong University School of Medicine,Shanghai,China7.Department of Pathophysiology,Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education,Shanghai Jiao Tong University School of Medicine,Shanghai,China;University of Michigan-Shanghai Jiao Tong University Joint Institute,Shanghai Jiao Tong University,Shanghai,China;Department of Biomedical Engineering,University of Michigan,Ann Arbor,Michigan,USA8.Research Center of Chinese Herbal Resources Science and Engineering,School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou,China9.Beijing Neurosurgical Institute,Capital Medical University,Beijing,China;China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital,Capital Medical University,Beijing,China;Department of Radiotherapy,Beijing Tiantan Hospital,Capital Medical University,Beijing,China10.Department of NeuroPathology,Sanbo Brain Hospital,Capital Medical University,Beijing,China11.College of Life Sciences,University of Chinese Academy of Sciences,Beijing,China12.Beijing Neurosurgical Institute,Capital Medical University,Beijing,China;China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital,Capital Medical University,Beijing,China;Department of Radiotherapy,Beijing Tiantan Hospital,Capital Medical University,Beijing,China;Chinese Institute for Medical Research,Beijing,China13.BGI-Shenzhen,Shenzhen,China
摘要：Background:Medulloblastoma(MB)is one of the most common malignant brain tu-mors 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 se-quencing.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 be-tween tumor and TME cells.
机标关键词：identifiesmedulloblastomapatient-derivedrecapitulatedsequencingsingle-cellsubcutaneoustranscriptomic
论文发表日期：2025-03-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：15( 458-472 )
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