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

Background: Oct4 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.
Results: By 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.
Conclusions: These 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.