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

Qiang Zhang, Sai Ma, Zhengzhi Liu, Bohan Zhu, Zirui Zhou, Gaoshan Li, J. Javier Meana, Javier González-Maeso and Chang Lu ()
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Qiang Zhang: Virginia Tech
Sai Ma: Virginia Tech
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

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40411-w

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