Bianchi, AgostinaScherer, MichaelZaurín Quer, RoserQuililan, KimberlyVelten, LarsBeekman, Renée2023-01-232023-01-232022Bianchi A, Scherer M, Zaurin R, Quililan K, Velten L, Beekman R. scTAM-seq enables targeted high-confidence analysis of DNA methylation in single cells. Genome Biol. 2022 Oct 28;23(1):229. DOI: 10.1186/s13059-022-02796-71474-7596http://hdl.handle.net/10230/55374Single-cell DNA methylation profiling currently suffers from excessive noise and/or limited cellular throughput. We developed scTAM-seq, a targeted bisulfite-free method for profiling up to 650 CpGs in up to 10,000 cells per experiment, with a dropout rate as low as 7%. We demonstrate that scTAM-seq can resolve DNA methylation dynamics across B-cell differentiation in blood and bone marrow, identifying intermediate differentiation states that were previously masked. scTAM-seq additionally queries surface-protein expression, thus enabling integration of single-cell DNA methylation information with cell atlas data. In summary, scTAM-seq is a high-throughput, high-confidence method for analyzing DNA methylation at single-CpG resolution across thousands of single cells.application/pdfeng© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data mainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s13059-022-02796-7DNA methylationEpigeneticsHematopoiesisMulti-omic analysisSingle-cell profilinginfo:eu-repo/semantics/openAccess