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Droplet-based bisulfite sequencing for high-throughput profiling of single-cell DNA methylomes

Author

Listed:
  • Qiang Zhang

    (Virginia Tech)

  • Sai Ma

    (Virginia Tech
    Icahn School of Medicine at Mount Sinai)

  • Zhengzhi Liu

    (Virginia Tech)

  • Bohan Zhu

    (Virginia Tech)

  • Zirui Zhou

    (Virginia Tech)

  • Gaoshan Li

    (Virginia Tech)

  • J. Javier Meana

    (University of the Basque Country UPV/EHU, CIBERSAM, Biocruces Health Research Institute)

  • Javier González-Maeso

    (Virginia Commonwealth University School of Medicine)

  • Chang Lu

    (Virginia Tech)

Abstract

The genome-wide DNA methylation profile, or DNA methylome, is a critical component of the overall epigenomic landscape that modulates gene activities and cell fate. Single-cell DNA methylomic studies offer unprecedented resolution for detecting and profiling cell subsets based on methylomic features. However, existing single-cell methylomic technologies are based on use of tubes or well plates and these platforms are not easily scalable for handling a large number of single cells. Here we demonstrate a droplet-based microfluidic technology, Drop-BS, to construct single-cell bisulfite sequencing libraries for DNA methylome profiling. Drop-BS takes advantage of the ultrahigh throughput offered by droplet microfluidics to prepare bisulfite sequencing libraries of up to 10,000 single cells within 2 days. We apply the technology to profile mixed cell lines, mouse and human brain tissues to reveal cell type heterogeneity. Drop-BS offers a promising solution for single-cell methylomic studies requiring examination of a large cell population.

Suggested Citation

  • Qiang Zhang & Sai Ma & Zhengzhi Liu & Bohan Zhu & Zirui Zhou & Gaoshan Li & J. Javier Meana & Javier González-Maeso & Chang Lu, 2023. "Droplet-based bisulfite sequencing for high-throughput profiling of single-cell DNA methylomes," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40411-w
    DOI: 10.1038/s41467-023-40411-w
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    1. Matthew D. Schultz & Yupeng He & John W. Whitaker & Manoj Hariharan & Eran A. Mukamel & Danny Leung & Nisha Rajagopal & Joseph R. Nery & Mark A. Urich & Huaming Chen & Shin Lin & Yiing Lin & Inkyung J, 2015. "Human body epigenome maps reveal noncanonical DNA methylation variation," Nature, Nature, vol. 523(7559), pages 212-216, July.
    2. Kyle J. Travaglini & Ahmad N. Nabhan & Lolita Penland & Rahul Sinha & Astrid Gillich & Rene V. Sit & Stephen Chang & Stephanie D. Conley & Yasuo Mori & Jun Seita & Gerald J. Berry & Joseph B. Shrager , 2020. "A molecular cell atlas of the human lung from single-cell RNA sequencing," Nature, Nature, vol. 587(7835), pages 619-625, November.
    3. Giacomo Cavalli & Edith Heard, 2019. "Advances in epigenetics link genetics to the environment and disease," Nature, Nature, vol. 571(7766), pages 489-499, July.
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