Bisulfite-free epigenomics and genomics of single cells through methylation-sensitive restriction

Christoph Niemöller; Julius Wehrle; Julian Riba; Rainer Claus; Nathalie Renz; Janika Rhein; Sabine Bleul; Juliane M Stosch; Justus Duyster; Christoph Plass; Pavlo Lutsik; Daniel B Lipka; Michael Lübbert; Heiko Becker

doi:10.1038/s42003-021-01661-w

Bisulfite-free epigenomics and genomics of single cells through methylation-sensitive restriction

Commun Biol. 2021 Feb 1;4(1):153. doi: 10.1038/s42003-021-01661-w.

Authors

Christoph Niemöller^#^{1

2

3

4}, Julius Wehrle^#^{1

2

5}, Julian Riba⁶, Rainer Claus^{1

2

7}, Nathalie Renz^{1

2

7}, Janika Rhein^{1

2}, Sabine Bleul^{1

2}, Juliane M Stosch^{1

2

4}, Justus Duyster^{1

2

3}, Christoph Plass⁸, Pavlo Lutsik⁸, Daniel B Lipka⁹, Michael Lübbert^{1

2

3}, Heiko Becker^{10

11

12}

Affiliations

¹ Department of Medicine I, Medical Center - University of Freiburg, Freiburg, Germany.
² Faculty of Medicine, University of Freiburg, Freiburg, Germany.
³ German Cancer Consortium (DKTK) partner site, Freiburg, Germany.
⁴ Faculty of Biology, University of Freiburg, Freiburg, Germany.
⁵ Institute of Digitalization in Medicine, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁶ Laboratory for MEMS Applications, Department of Microsystems Engineering - IMTEK, University of Freiburg, Freiburg, Germany.
⁷ Department of Hematology and Oncology, Augsburg University Medical Center, Augsburg, Germany.
⁸ Division of Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁹ Section Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center (DKFZ) & National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany.
¹⁰ Department of Medicine I, Medical Center - University of Freiburg, Freiburg, Germany. [email protected].
¹¹ Faculty of Medicine, University of Freiburg, Freiburg, Germany. [email protected].
¹² German Cancer Consortium (DKTK) partner site, Freiburg, Germany. [email protected].

^# Contributed equally.

Abstract

Single-cell multi-omics are powerful means to study cell-to-cell heterogeneity. Here, we present a single-tube, bisulfite-free method for the simultaneous, genome-wide analysis of DNA methylation and genetic variants in single cells: epigenomics and genomics of single cells analyzed by restriction (epi-gSCAR). By applying this method, we obtained DNA methylation measurements of up to 506,063 CpGs and up to 1,244,188 single-nucleotide variants from single acute myeloid leukemia-derived cells. We demonstrate that epi-gSCAR generates accurate and reproducible measurements of DNA methylation and allows to differentiate between cell lines based on the DNA methylation and genetic profiles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
CpG Islands
DNA Methylation*
Epigenesis, Genetic*
Epigenome*
Epigenomics*
Gene Expression Regulation, Neoplastic
High-Throughput Nucleotide Sequencing
Humans
Leukemia, Myeloid, Acute / genetics*
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
RNA-Seq
Reproducibility of Results
Single-Cell Analysis*