Sequencing the DNA and mRNA from the same single cell

Single-cell genome and transcriptome data can address many questions, including somatic variation, meiotic recombination and cell-to-cell heterogeneity of expression, and techniques for single-cell sequencing have developed rapidly in recent years. Here, we further adapted this technology by performing simultaneous single-cell exome and transcriptome profiling on individual mouse oocytes. In brief, we physically separated the oocyte nuclei and cytoplasm using a micromanipulator. We then conducted exome-sequencing on the isolated nuclei and mRNA-sequencing on the enucleated cytoplasm. Combined analysis of the simultaneously derived sequencing data disclosed a high heterozygous recombination rate during oocyte meiosis, and genomic and transcriptomic heterogeneity among individual oocytes. This approach provides unprecedented opportunities to study RNA editing of single oocytes. Overall design: Sequencing the DNA and mRNA from 6 single mouse secondary oocytes