Ever wanted to be able to do two things at the same time? Like work and have a social life? Eat pizza and still fit in your new purchases? Pat your head and rub your belly? While these highly important combinations remain almost impossible (at least for the EpiGenie staff), a stellar cast of scientists have recently had a notable double success. They have devised a strategy to generate both epigenetic and transcriptional data from the same single stem cell.
This technique – single cell methylome and transcriptome sequencing (scM&T-seq) – combines ideas from two previously reported sequencing strategies: single-cell bisulfite sequencing (scBS-seq) and parallel genome and transcriptome sequencing (G&T-seq). The second technique relies on the physical separation of RNA and DNA, so one could take advantage of this to study DNA methylation following bisulfite conversion while retaining transcriptomic information from the RNA.
This is exactly what is described in a Nature Materials study from the laboratories of Thierry Voet (Sanger Institute), Oliver Stegle (EMBL-EBI), Gavin Kelsey and Wolf Reik (Babraham Institute) as a means to associate transcriptional and epigenetic variation in single stem cells.
This new study shows:
- Generation of high-quality parallel data profiles of single mouse embryonic stem cells (mESCs).
- Results confirm previously described correlations between DNA methylation and transcriptional activity found using stand-alone analyses.
- Discovery of new associations between the transcriptional activities of pluripotency-associated genes and the heterogeneous nature of DNA methylation at their distal regulatory elements in stem cells.
- As an example, Esrrb expression decreases upon higher methylation of distal regulatory sites, such as low-methylation regions (LMRs) and p300 sites overlapping super-enhancers.
- The study demonstrated similar data for 516 genes whose expression correlated with overall methylation level.
The authors point to the ability of this technique to analyze in depth the connectivity between transcriptional and DNA methylation heterogeneity in single stem cells and, in the future, identify the factors behind the factors which influence this relationship.
So, maybe you should drink your coffee and read this new paper at Nature Materials, Jan 2016? See! You are well on your way to halving your workload already today!