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, Chang Lu

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish
Article number4672
JournalNature Communications
Issue number1
StatePublished - Dec 2023


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