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.

Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity