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Related Experiment Video

Updated: Jan 9, 2026

Genome-wide Purification of Extrachromosomal Circular DNA from Eukaryotic Cells
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scCirclehunter delineates ecDNA-containing cells using single-cell ATAC-seq, with a focus on glioblastoma.

Rong Jiang1, Zhengmao Lu2, Fang Li1

  • 1MOE Key Laboratory of Geriatric Diseases and Immunology, School of Basic Medical Sciences, Soochow University, Suzhou, Jiangsu, China.

Cell Discovery
|December 8, 2025
PubMed
Summary

Extrachromosomal DNA (ecDNA) drives cancer heterogeneity and poor prognosis. Our new scCirclehunter tool analyzes patient ecDNA at single-cell resolution, revealing its role in glioblastoma progression and cell evolution.

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Area of Science:

  • Genomics
  • Cancer Biology
  • Single-cell analysis

Background:

  • Extrachromosomal DNA (ecDNA) is a key driver of tumor heterogeneity and poor prognosis in cancer.
  • Limited single-cell resolution studies exist for patient-derived ecDNA.

Purpose of the Study:

  • Introduce scCirclehunter, a novel framework to identify ecDNA from single-cell ATAC-seq (scATAC-seq) data.
  • Analyze ecDNA heterogeneity and cellular trajectories in glioblastoma (GBM) patients.
  • Investigate mechanisms of ecDNA-driven tumor progression and potential links to mitochondrial transfer.

Main Methods:

  • Developed scCirclehunter for ecDNA identification and cell population assignment from scATAC-seq data.
  • Applied scCirclehunter to glioblastoma datasets.
  • Integrated scRNA-seq data for mechanistic insights and analysis of ecNR2E1.
  • Examined intercellular heterogeneity and cell trajectories.

Main Results:

  • Uncovered significant inter-cellular heterogeneity of ecDNA-carrying cells across GBM patients.
  • Traced malignant cell trajectories in patients with multiple ecDNAs.
  • Demonstrated ecDNA drives GBM progression via multiple mechanisms, exemplified by ecNR2E1.
  • Observed a potential link between ecDNA and increased mitochondrial transfer frequency.

Conclusions:

  • scCirclehunter offers a powerful framework for single-cell precision analysis of patient-specific ecDNAs.
  • Provides critical insights into the role of ecDNA-carrying cells in driving GBM heterogeneity.
  • Highlights ecDNA as a significant factor in glioblastoma pathogenesis and progression.