scCirclehunter delineates ecDNA-containing cells using single-cell ATAC-seq, with a focus on glioblastoma.
Cell Discov, 2025/12/09;11(1):98.
Jiang R[1], Lu Z[2], Li F[1], Zhu Y[1], Yang M[1], Zhang S[1], Wu P[3], Gong C[3], Fei Y[1], Sang Y[4], Huang Y[5], Guo JJ[6], Huang M[7]
Affiliations
PMID: 41360770DOI: 10.1038/s41421-025-00842-9
Abstract
In cancer, extrachromosomal DNA (ecDNA) contributes to tumor heterogeneity and is associated with poor prognosis, but studies on patient-derived ecDNA are relatively limited at single-cell resolution. Here, we introduce scCirclehunter, a framework designed to identify ecDNA from scATAC-seq data and assign ecDNA to specific cell populations. Leveraging scCirclehunter and available glioblastoma (GBM) datasets, we uncover the inter-cellular heterogeneity of ecDNA-carrying cells across GBM patients and trace the trajectories of malignant cells within a single patient that harbors multiple ecDNAs. By integrating scRNA-seq data, we use ecNR2E1 as an example to demonstrate that ecDNA drives tumor progression in GBM through several mechanisms. Additionally, our findings suggest a potential link between ecDNA and increased mitochondrial transfer frequency. Overall, scCirclehunter provides a novel framework for analyzing patient-specific ecDNAs with single-cell precision, offering insights into the role of ecDNA-carrying cells in driving GBM heterogeneity.
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download