Reconstitution of the oocyte transcriptional network with transcription factors

Abstract

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 1 , 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.

WNT signaling in pre-granulosa cells is required for ovarian folliculogenesis and female fertility

“…Recent progress in the field of in vitro gametogenesis (IVG) has had a great impact on reproductive biology and medicine ( Hikabe et al, 2016 ; Hamazaki et al, 2021 ). Fully developed oocytes can now be obtained from embryonic stem cells or induced pluripotent stem cells of mice by the application of IVG techniques.…”

Rewinding Extinction in the Northern White Rhinoceros: Genetically Diverse Induced Pluripotent Stem Cell Bank for Genetic Rescue

“…Recent research has reported the generation of functional gametes from iPSCs in mouse [20], and key PGC developmental pathways have been identified in human [21,53,54] and cynomolgus monkey [44]. Recently, transcription factor-driven oocyte development from PSCs has been reported [55].…”

Figla promotes secondary follicle growth in mature mice

“…In the present study, relative expression levels of some of Figla downstream genes were significantly different between secondary follicle oocytes of pre-/mature mice, supporting that secondary follicle growth in mature mice may be regulated in part by Figla. However, as folliculogenesis is a highly complex process 48 that requires appropriate set of genes to orchestrate its growth 49 , there is a limitation for discussing it with a single transcription factor.…”