Gatekeeper of pluripotency: A common Oct4 transcriptional network operates in mouse eggs and embryonic stem cells

Abstract

BackgroundOct4 is a key factor of an expanded transcriptional network (Oct4-TN) that governs pluripotency and self-renewal in embryonic stem cells (ESCs) and in the inner cell mass from which ESCs are derived. A pending question is whether the establishment of the Oct4-TN initiates during oogenesis or after fertilisation. To this regard, recent evidence has shown that Oct4 controls a poorly known Oct4-TN central to the acquisition of the mouse egg developmental competence. The aim of this study was to investigate the identity and extension of this maternal Oct4-TN, as much as whether its presence is circumscribed to the egg or maintained beyond fertilisation.ResultsBy comparing the genome-wide transcriptional profile of developmentally competent eggs that express the OCT4 protein to that of developmentally incompetent eggs in which OCT4 is down-regulated, we unveiled a maternal Oct4-TN of 182 genes. Eighty of these transcripts escape post-fertilisation degradation and represent the maternal Oct4-TN inheritance that is passed on to the 2-cell embryo. Most of these 80 genes are expressed in cancer cells and 37 are notable companions of the Oct4 transcriptome in ESCs.ConclusionsThese results provide, for the first time, a developmental link between eggs, early preimplantation embryos and ESCs, indicating that the molecular signature that characterises the ESCs identity is rooted in oogenesis. Also, they contribute a useful resource to further study the mechanisms of Oct4 function and regulation during the maternal-to-embryo transition and to explore the link between the regulation of pluripotency and the acquisition of de-differentiation in cancer cells.

OCT4 and the acquisition of oocyte developmental competence during folliculogenesis

“…5). Interestingly, the majority of these genes are down-regulated in MII ctrl oocytes, whereas after fertilisation, the same genes result up-regulated in 2-cell ctrl embryos, an expression behaviour that is confirmed by the immunoanalysis of the proteins of two of these genes (DNMT3L and RSP20; Zuccotti et al, 2011).…”

“…3) (Zuccotti et al, 2011). Gene onthology enrichment analysis of the function of these 197 genes assigned them to several major biological processes, including pluripotency, chromatin organisation, apoptosis, subcortical maternal complex, transcription factorscancer, translation-cancer, oxidative phosphorylation, porphyrin metabolism, anion exchange, TGF-b signalling, copper distribution, regulation of transcription, protein phosphorilation, cell cycle, protein assembly and signal transduction (Fig.…”

The control of mitochondrial DNA replication during development and tumorigenesis

“…In the absence of OCT4, the pluripotent cells of the mouse ICM differentiate into the trophectoderm, which contains the precursor cells of the placenta and are first identifiable at the blastocyst stage. However, if Oct4 is expressed above the endogenous level, pluripotent ES cells differentiate into the extra‐embryonic endoderm lineage . SOX2 belongs to the SRY‐related HMG box (SOX) family and is a transcription factor with a single HMG DNA‐binding domain.…”

Knowledge-based bioinformatics for the study of mammalian oocytes

“…For example, Zuccotti et al, (2011) expanded the set of genes initially selected relying on the expression values considering the information extracted from GO and the literature. The knowledge bases and the methods for extracting and representing the knowledge were then used to produce a OCT4 transcriptional network.…”