PUBLICATION
Clinically relevant orthotopic xenograft models of patient-derived glioblastoma in zebrafish
- Authors
- Ai, X., Ye, Z., Xiao, C., Zhong, J., Lancman, J.J., Chen, X., Pan, X., Yang, Y., Zhou, L., Wang, X., Shi, H., Zhang, D., Yao, Y., Cao, D., Zhao, C.
- ID
- ZDB-PUB-220225-4
- Date
- 2022
- Source
- Disease models & mechanisms 15(4): (Journal)
- Registered Authors
- Lancman, Joseph
- Keywords
- Blood-brain barrier, Glioblastoma, Heterogeneity, PDOX., PDX, Zebrafish
- Datasets
- GEO:GSE147526
- MeSH Terms
-
- Animals
- Brain Neoplasms*/pathology
- Disease Models, Animal
- Glioblastoma*/pathology
- Heterografts
- Humans
- Mammals
- Mice
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 35199829 Full text @ Dis. Model. Mech.
Citation
Ai, X., Ye, Z., Xiao, C., Zhong, J., Lancman, J.J., Chen, X., Pan, X., Yang, Y., Zhou, L., Wang, X., Shi, H., Zhang, D., Yao, Y., Cao, D., Zhao, C. (2022) Clinically relevant orthotopic xenograft models of patient-derived glioblastoma in zebrafish. Disease models & mechanisms. 15(4).
Abstract
An accurate prediction of the intracranial infiltration tendency and drug response of individual Glioblastoma (GBM) cells is essential for personalized prognosis and treatment for this disease. However, the clinical utility of mouse PDOX models remains limited given current technical constraints including difficulty in generating sufficient sample numbers from small tissue samples and a long latency period for results. To overcome these issues, we establish zebrafish GBM xenografts of diverse origin, which can tolerate intracranial engraftment and maintain their unique histological features. Subsequent single cell RNA-seq (scRNA-seq) analysis confirms significant transcriptional identity resemble invading GBM microtumors observed in the proportionally larger brains of model animals and humans. Endothelial scRNA-seq confirms zebrafish blood-brain-barrier is homologous to the mammalian. Finally, we establish a rapid and efficient zebrafish PDOX (zPDOX) model, which can predict long-term outcomes of GBM patients within 20 days. zPDOX provides a novel avenue for precision medicine of GBM, especially for the evaluation of intracranial infiltration tendency and prediction of individual drug sensitivity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping