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scCircle-seq unveils the diversity and complexity of extrachromosomal circular DNAs in single cells

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Listed:
  • Jinxin Phaedo Chen

    (Tumor and Cell Biology, Karolinska Institutet
    Science for Life Laboratory, Tomtebodavägen 23A)

  • Constantin Diekmann

    (Tumor and Cell Biology, Karolinska Institutet
    Science for Life Laboratory, Tomtebodavägen 23A)

  • Honggui Wu

    (Peking University
    Peking University)

  • Chong Chen

    (West China Hospital, Sichuan University)

  • Giulia Chiara

    (Viale Rita Levi-Montalcini 1)

  • Enrico Berrino

    (FPO – IRCCS, Candiolo, SP142, km 3,95
    University of Turin)

  • Konstantinos L. Georgiadis

    (Science for Life Laboratory, Tomtebodavägen 23A
    Karolinska Institutet)

  • Britta A. M. Bouwman

    (Tumor and Cell Biology, Karolinska Institutet
    Science for Life Laboratory, Tomtebodavägen 23A)

  • Mohit Virdi

    (Viale Rita Levi-Montalcini 1)

  • Luuk Harbers

    (Tumor and Cell Biology, Karolinska Institutet
    Science for Life Laboratory, Tomtebodavägen 23A)

  • Sara Erika Bellomo

    (FPO – IRCCS, Candiolo, SP142, km 3,95)

  • Caterina Marchiò

    (FPO – IRCCS, Candiolo, SP142, km 3,95
    University of Turin)

  • Magda Bienko

    (Tumor and Cell Biology, Karolinska Institutet
    Science for Life Laboratory, Tomtebodavägen 23A
    Viale Rita Levi-Montalcini 1)

  • Nicola Crosetto

    (Tumor and Cell Biology, Karolinska Institutet
    Science for Life Laboratory, Tomtebodavägen 23A
    Viale Rita Levi-Montalcini 1)

Abstract

Extrachromosomal circular DNAs (eccDNAs) have emerged as important intra-cellular mobile genetic elements that affect gene copy number and exert in trans regulatory roles within the cell nucleus. Here, we describe scCircle-seq, a method for profiling eccDNAs and unraveling their diversity and complexity in single cells. We implement and validate scCircle-seq in normal and cancer cell lines, demonstrating that most eccDNAs vary largely between cells and are stochastically inherited during cell division, although their genomic landscape is cell type-specific and can be used to accurately cluster cells of the same origin. eccDNAs are preferentially produced from chromatin regions enriched in H3K9me3 and H3K27me3 histone marks and are induced during replication stress conditions. Concomitant sequencing of eccDNAs and RNA from the same cell uncovers the absence of correlation between eccDNA copy number and gene expression levels, except for a few oncogenes, including MYC, contained within a large eccDNA in colorectal cancer cells. Lastly, we apply scCircle-seq to one prostate cancer and two breast cancer specimens, revealing cancer-specific eccDNA landscapes and a higher propensity of eccDNAs to form in amplified genomic regions. scCircle-seq is a scalable tool that can be used to dissect the complexity of eccDNAs across different cell and tissue types, and further expands the potential of eccDNAs for cancer diagnostics.

Suggested Citation

  • Jinxin Phaedo Chen & Constantin Diekmann & Honggui Wu & Chong Chen & Giulia Chiara & Enrico Berrino & Konstantinos L. Georgiadis & Britta A. M. Bouwman & Mohit Virdi & Luuk Harbers & Sara Erika Bellom, 2024. "scCircle-seq unveils the diversity and complexity of extrachromosomal circular DNAs in single cells," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45972-y
    DOI: 10.1038/s41467-024-45972-y
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    References listed on IDEAS

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    1. Yuangao Wang & Meng Wang & Mohamed Nadhir Djekidel & Huan Chen & Di Liu & Frederick W. Alt & Yi Zhang, 2021. "eccDNAs are apoptotic products with high innate immunostimulatory activity," Nature, Nature, vol. 599(7884), pages 308-314, November.
    2. Ofer Shoshani & Simon F. Brunner & Rona Yaeger & Peter Ly & Yael Nechemia-Arbely & Dong Hyun Kim & Rongxin Fang & Guillaume A. Castillon & Miao Yu & Julia S. Z. Li & Ying Sun & Mark H. Ellisman & Bing, 2021. "Chromothripsis drives the evolution of gene amplification in cancer," Nature, Nature, vol. 591(7848), pages 137-141, March.
    3. Ofer Shoshani & Simon F. Brunner & Rona Yaeger & Peter Ly & Yael Nechemia-Arbely & Dong Hyun Kim & Rongxin Fang & Guillaume A. Castillon & Miao Yu & Julia S. Z. Li & Ying Sun & Mark H. Ellisman & Bing, 2021. "Publisher Correction: Chromothripsis drives the evolution of gene amplification in cancer," Nature, Nature, vol. 591(7850), pages 19-19, March.
    4. Aakash Basu & Dmitriy G. Bobrovnikov & Zan Qureshi & Tunc Kayikcioglu & Thuy T. M. Ngo & Anand Ranjan & Sebastian Eustermann & Basilio Cieza & Michael T. Morgan & Miroslav Hejna & H. Tomas Rube & Karl, 2021. "Measuring DNA mechanics on the genome scale," Nature, Nature, vol. 589(7842), pages 462-467, January.
    5. Sihan Wu & Kristen M. Turner & Nam Nguyen & Ramya Raviram & Marcella Erb & Jennifer Santini & Jens Luebeck & Utkrisht Rajkumar & Yarui Diao & Bin Li & Wenjing Zhang & Nathan Jameson & M. Ryan Corces &, 2019. "Circular ecDNA promotes accessible chromatin and high oncogene expression," Nature, Nature, vol. 575(7784), pages 699-703, November.
    6. Konstantin Helmsauer & Maria E. Valieva & Salaheddine Ali & Rocío Chamorro González & Robert Schöpflin & Claudia Röefzaad & Yi Bei & Heathcliff Dorado Garcia & Elias Rodriguez-Fos & Montserrat Puiggrò, 2020. "Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    7. King L. Hung & Kathryn E. Yost & Liangqi Xie & Quanming Shi & Konstantin Helmsauer & Jens Luebeck & Robert Schöpflin & Joshua T. Lange & Rocío Chamorro González & Natasha E. Weiser & Celine Chen & Mar, 2021. "ecDNA hubs drive cooperative intermolecular oncogene expression," Nature, Nature, vol. 600(7890), pages 731-736, December.
    8. Eleni Gelali & Gabriele Girelli & Masahiro Matsumoto & Erik Wernersson & Joaquin Custodio & Ana Mota & Maud Schweitzer & Katalin Ferenc & Xinge Li & Reza Mirzazadeh & Federico Agostini & John P. Schel, 2019. "iFISH is a publically available resource enabling versatile DNA FISH to study genome architecture," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    9. Fu Yang & Weijia Su & Oliver W. Chung & Lauren Tracy & Lu Wang & Dale A. Ramsden & ZZ Zhao Zhang, 2023. "Retrotransposons hijack alt-EJ for DNA replication and eccDNA biogenesis," Nature, Nature, vol. 620(7972), pages 218-225, August.
    10. Darlan C. Minussi & Michael D. Nicholson & Hanghui Ye & Alexander Davis & Kaile Wang & Toby Baker & Maxime Tarabichi & Emi Sei & Haowei Du & Mashiat Rabbani & Cheng Peng & Min Hu & Shanshan Bai & Yu-w, 2021. "Breast tumours maintain a reservoir of subclonal diversity during expansion," Nature, Nature, vol. 592(7853), pages 302-308, April.
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