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.

Single-cell DNA methylomic studies offer high resolution to differentiate cell subsets based on their epigenomic features. Here, the authors demonstrate Drop-BS, a droplet-based single-cell bisulfite sequencing library preparation method, for DNA methylome profiling.

Details

Title
Droplet-based bisulfite sequencing for high-throughput profiling of single-cell DNA methylomes
Author
Zhang, Qiang 1 ; Ma, Sai 2   VIAFID ORCID Logo  ; Liu, Zhengzhi 3 ; Zhu, Bohan 1 ; Zhou, Zirui 1 ; Li, Gaoshan 1 ; Meana, J. Javier 4   VIAFID ORCID Logo  ; González-Maeso, Javier 5 ; Lu, Chang 1   VIAFID ORCID Logo 

 Virginia Tech, Department of Chemical Engineering, Blacksburg, USA (GRID:grid.438526.e) (ISNI:0000 0001 0694 4940) 
 Virginia Tech, Department of Biomedical Engineering and Mechanics, Blacksburg, USA (GRID:grid.438526.e) (ISNI:0000 0001 0694 4940); Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351) 
 Virginia Tech, Department of Biomedical Engineering and Mechanics, Blacksburg, USA (GRID:grid.438526.e) (ISNI:0000 0001 0694 4940) 
 University of the Basque Country UPV/EHU, CIBERSAM, Biocruces Health Research Institute, Department of Pharmacology, Leioa, Spain (GRID:grid.11480.3c) (ISNI:0000000121671098) 
 Virginia Commonwealth University School of Medicine, Department of Physiology and Biophysics, Richmond, USA (GRID:grid.224260.0) (ISNI:0000 0004 0458 8737) 
Pages
4672
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2845354608
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.