Parallel single-cell bisulfite- and RNA-sequencing link transcriptional and epigenetic heterogeneity [RNA-seq]

We report scM&T-seq, a method for parallel single-cell genome-wide methylome and transcriptome sequencing, allowing 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 reveals novel associations between heterogeneous methylation of distal regulatory elements and transcriptional heterogeneity of key pluripotency genes. E14 ES cells were grown in either serum/LIF or 2i culture conditions and separated into single cells. RNA-Seq or Bisulfite-Seq libraries were prepared. This Series includes only the RNA-Seq data. The list of 61 samples that passed QC in both BS-seq and RNA-seq is included in "Supplementary Table 1" of the associated manuscript.