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Exploring the cellular landscape of circular RNAs using full-length single-cell RNA sequencing

Author

Listed:
  • Wanying Wu

    (Beijing Institutes of Life Science, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Jinyang Zhang

    (Beijing Institutes of Life Science, Chinese Academy of Sciences)

  • Xiaofei Cao

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Zhengyi Cai

    (Beijing Institutes of Life Science, Chinese Academy of Sciences)

  • Fangqing Zhao

    (Beijing Institutes of Life Science, Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    University of Chinese Academy of Sciences, Chinese Academy of Sciences
    State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences)

Abstract

Previous studies have demonstrated the highly specific expression of circular RNAs (circRNAs) in different tissues and organisms, but the cellular architecture of circRNA has never been fully characterized. Here, we present a collection of 171 full-length single-cell RNA-seq datasets to explore the cellular landscape of circRNAs in human and mouse tissues. Through large-scale integrative analysis, we identify a total of 139,643 human and 214,747 mouse circRNAs in these scRNA-seq libraries. We validate the detected circRNAs with the integration of 11 bulk RNA-seq based resources, where 216,602 high-confidence circRNAs are uniquely detected in the single-cell cohort. We reveal the cell-type-specific expression pattern of circRNAs in brain samples, developing embryos, and breast tumors. We identify the uniquely expressed circRNAs in different cell types and validate their performance in tumor-infiltrating immune cell composition deconvolution. This study expands our knowledge of circRNA expression to the single-cell level and provides a useful resource for exploring circRNAs at this unprecedented resolution.

Suggested Citation

  • Wanying Wu & Jinyang Zhang & Xiaofei Cao & Zhengyi Cai & Fangqing Zhao, 2022. "Exploring the cellular landscape of circular RNAs using full-length single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30963-8
    DOI: 10.1038/s41467-022-30963-8
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    References listed on IDEAS

    as
    1. Jinyang Zhang & Shuai Chen & Jingwen Yang & Fangqing Zhao, 2020. "Accurate quantification of circular RNAs identifies extensive circular isoform switching events," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Ruijiao Xin & Yan Gao & Yuan Gao & Robert Wang & Kathryn E. Kadash-Edmondson & Bo Liu & Yadong Wang & Lan Lin & Yi Xing, 2021. "isoCirc catalogs full-length circular RNA isoforms in human transcriptomes," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    3. Peng He & Brian A. Williams & Diane Trout & Georgi K. Marinov & Henry Amrhein & Libera Berghella & Say-Tar Goh & Ingrid Plajzer-Frick & Veena Afzal & Len A. Pennacchio & Diane E. Dickel & Axel Visel &, 2020. "The changing mouse embryo transcriptome at whole tissue and single-cell resolution," Nature, Nature, vol. 583(7818), pages 760-767, July.
    4. Benyu Liu & Buqing Ye & Xiaoxiao Zhu & Liuliu Yang & Huimu Li & Nian Liu & Pingping Zhu & Tiankun Lu & Luyun He & Yong Tian & Zusen Fan, 2020. "An inducible circular RNA circKcnt2 inhibits ILC3 activation to facilitate colitis resolution," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    5. Yuan Gao & Jinfeng Wang & Yi Zheng & Jinyang Zhang & Shuai Chen & Fangqing Zhao, 2016. "Comprehensive identification of internal structure and alternative splicing events in circular RNAs," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
    6. Mihriban Karaayvaz & Simona Cristea & Shawn M. Gillespie & Anoop P. Patel & Ravindra Mylvaganam & Christina C. Luo & Michelle C. Specht & Bradley E. Bernstein & Franziska Michor & Leif W. Ellisen, 2018. "Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    7. Tetsutaro Hayashi & Haruka Ozaki & Yohei Sasagawa & Mana Umeda & Hiroki Danno & Itoshi Nikaido, 2018. "Single-cell full-length total RNA sequencing uncovers dynamics of recursive splicing and enhancer RNAs," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    8. Lasse S. Kristensen & Karoline K. Ebbesen & Martin Sokol & Theresa Jakobsen & Ulrik Korsgaard & Ann C. Eriksen & Thomas B. Hansen & Jørgen Kjems & Henrik Hager, 2020. "Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
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    1. Xianjun Dong & Yunfei Bai & Zhixiang Liao & David Gritsch & Xiaoli Liu & Tao Wang & Rebeca Borges-Monroy & Alyssa Ehrlich & Geidy E. Serrano & Mel B. Feany & Thomas G. Beach & Clemens R. Scherzer, 2023. "Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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