Affiliation:
1. The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation State Key Laboratory of Physical Chemistry of Solid Surfaces Key Laboratory for Chemical Biology of Fujian Province Collaborative Innovation Center of Chemistry for Energy Materials Department of Chemical Biology College of Chemistry and Chemical Engineering Xiamen University Xiamen 361005 P. R. China
2. State Key Laboratory of Genetic Engineering School of Life Sciences Fudan University Shanghai 200433 P. R. China
3. Institute of Molecular Medicine Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200120 P. R. China
Abstract
AbstractSimultaneous profiling of DNA methylation and gene expression within single cells is a powerful technology to dissect complex gene regulatory network of cells. However, existing methods are based on picking a single‐cell in a tube and split single‐cell lysate into two parts for transcriptome and methylome library construction, respectively, which is costly and cumbersome. Here, DIRECT is proposed, a digital microfluidics‐based method for high‐efficiency single‐cell isolation and simultaneous analysis of the methylome and transcriptome in a single library construction. The accuracy of DIRECT is demonstrated in comparison with bulk and single‐omics data, and the high CpG site coverage of DIRECT allows for precise analysis of copy number variation information, enabling expansion of single cell analysis from two‐ to three‐omics. By applying DIRECT to monitor the dynamics of mouse embryonic stem cell differentiation, the relationship between DNA methylation and changes in gene expression during differentiation is revealed. DIRECT enables accurate, robust, and reproducible single‐cell DNA methylation and gene expression co‐analysis in a more cost‐effective, simpler library preparation and automated manner, broadening the application scenarios of single‐cell multi‐omics analysis and revealing a more comprehensive and fine‐grained map of cellular regulatory landscapes.
Funder
National Natural Science Foundation of China
National Key Research and Development Program of China
Fundamental Research Funds for the Central Universities
Subject
General Materials Science,General Chemistry
Cited by
1 articles.
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