Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity

Parallel, genome-wide methylation and transcriptional profiling from a single cell (scM&T-seq) enables the discovery of associations between transcriptional and epigenetic variation. We report scM&T-seq, a method for parallel single-cell genome-wide methylome and transcriptome sequencing tha...

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Published inNature methods Vol. 13; no. 3; pp. 229 - 232
Main Authors Angermueller, Christof, Clark, Stephen J, Lee, Heather J, Macaulay, Iain C, Teng, Mabel J, Hu, Tim Xiaoming, Krueger, Felix, Smallwood, Sébastien A, Ponting, Chris P, Voet, Thierry, Kelsey, Gavin, Stegle, Oliver, Reik, Wolf
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.03.2016
Nature Publishing Group
Subjects
13/100
13/106
45/56
631/1647/2210/2213
631/1647/514/1949
631/208/199
631/337/176
Analysis
Animals
Base Sequence
Bioinformatics
Biological Microscopy
Biological Techniques
Biomedical Engineering/Biotechnology
brief-communication
Cells, Cultured
Cellular biology
Deoxyribonucleic acid
DNA
DNA sequencing
Embryonic stem cells
Embryonic Stem Cells - physiology
Embryos
Epigenesis, Genetic - genetics
Genetic transcription
Genomes
Heterogeneity
High-Throughput Nucleotide Sequencing - methods
Life Sciences
Methylation
Mice
Molecular Sequence Data
Nucleotide sequencing
Proteomics
Regulatory Elements, Transcriptional - genetics
Stem cells
Transcription Factors - genetics
United Kingdom
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Summary:Parallel, genome-wide methylation and transcriptional profiling from a single cell (scM&T-seq) enables the discovery of associations between transcriptional and epigenetic variation. We report scM&T-seq, a method for parallel single-cell genome-wide methylome and transcriptome sequencing that allows for the discovery of associations between transcriptional and epigenetic variation. Profiling of 61 mouse embryonic stem cells confirmed known links between DNA methylation and transcription. Notably, the method revealed previously unrecognized associations between heterogeneously methylated distal regulatory elements and transcription of key pluripotency genes.
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content type line 23
C.A. performed all statistical analyses of the data. H.J.L, I.C.M., S.C., S.S. developed the protocol and performed experiments. H.J.L, I.C.M., C.A., S.C., O.S., W.R., C.P.P. interpreted the results. M.J.T. contributed to method development. T.H. processed RNA-seq data. F.K. processed BS-seq data. W.R., G.K., I.C.M., & T.V. contributed protocols and reagents. H.J.L, I.C.M., W.R., T.V. conceived the project. W.R., O.S., T.V., G.K. jointly supervised the project. O.S., H.J.L, S.C., W.R., I.C.M, wrote the paper with input from all authors.
Author contributions
ISSN:1548-7091
1548-7105
DOI:10.1038/nmeth.3728