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<p>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.</p>

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scCirclehunter delineates ecDNA-containing cells using single-cell ATAC-seq, with a focus on glioblastoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月9日

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  • Rong Jiang,
  • Zhengmao Lu,
  • Fang Li,
  • Yibei Zhu,
  • Manqiu Yang,
  • Shufan Zhang,
  • Ping Wu,
  • Chengliang Gong,
  • Yiyuan Fei,
  • Yonghua Sang,
  • Yulun Huang,
  • Jiong Jiong Guo,
  • Moli Huang

摘要

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.