Single-Cell Whole-Genome Bisulfite Sequencing for Analysis of Epigenetic Heterogeneity. Mus musculus

We report a single-cell whole-genome bisulfite sequencing method (scBS-Seq) capable of accurately measuring DNA methylation at up to 36% of CpGs. We observed that ESCs grown in serum/LIF or 2i/LIF both display epigenetic heterogeneity, with “2i-like” cells present in serum cultures. In silico integration of 12 individual MII oocytes datasets recapitulates the whole DNA methylome, making scBS-Seq a versatile tool to explore DNA methylation in rare cells and heterogeneous populations. Overall design: scBS-Seq has been performed on mouse MII oocytes for technical validation and on mouse ESCs cultured in 2i/LIF and serum/LIF to investage epigenetic heterogeneity