DNA methylome analysis of directly induced oocyte-like cells (DIOLs)

During female germline development oocytes become a highly specialized cell type, and form a maternal cytoplasmic store of crucial factors during oocyte growth. Oocyte growth is triggered at the primordial-primary follicle transition accompanied with dynamic changes in gene expression, yet the gene regulatory network underpinning oocyte growth remains elusive. Here we identified a set of transcription factors sufficient to trigger oocyte growth. By dissection of the change in gene expression and functional screening using an in vitro oocyte development system, we identified 8 transcription factors, each of which was essential for the primordial-primary follicle transition. Surprisingly, enforced expression of these transcription factors swiftly converted pluripotent stem cells to oocyte-like cells that were competent for fertilization and subsequent cleavage. These transcription factor-induced oocyte-like cells were formed without PGC specification, epigenetic reprogramming or meiosis, establishing that oocyte growth and lineage-specific de novo DNA methylation is separable from the preceding epigenetic reprogramming in PGCs. This study identifies a core set of transcription factors for orchestrating oocyte growth, and also provides an alternative source of ooplasm, which is a unique material for reproductive biology and medicine. Overall design: paired-end PBAT sequence for whole genome methylome of directly induced oocyte-like cells (DIOLs)