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bioRxiv · 10.1101/2023.05.26.542421

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

Zhang, Q.·Ma, S.·Liu, Z.·Zhu, B.·Zhou, Z.·Li, G.·Meana, J. J.·Gonzalez-Maeso, J.·Lu, C.
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Abstract

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 all 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 d. We applied the technology to profile mixed cell lines, mouse and human brain tissues to reveal cell type heterogeneity. Drop-BS will pave the way for single-cell methylomic studies requiring examination of a large cell population.

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Zhang, Q., Ma, S., Liu, Z., Zhu, B., Zhou, Z., Li, G., Meana, J. J., Gonzalez-Maeso, J., Lu, C.. 2023-05-28. Droplet-based bisulfite sequencing for high-throughput profiling of single-cell DNA methylomes. https://doi.org/10.1101/2023.05.26.542421

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