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

• Published in: BMC genomics 2011-07, Vol.12 (1), p.1-13, Article 345
• Main Authors: Zuccotti, Maurizio, Merico, Valeria, Bellone, Michele, Mulas, Francesca, Sacchi, Lucia, Rebuzzini, Paola, Prigione, Alessandro, Redi, Carlo A, Bellazzi, Riccardo, Adjaye, James, Garagna, Silvia
• Format: Article
• Language: English
• Subjects: Animals; Down-Regulation; Embryonic development; Embryonic stem cells; Embryonic Stem Cells - metabolism; Female; Gene Expression Profiling; Gene Regulatory Networks; Genetic aspects; Genetic transcription; Mice; Multigene Family; Octamer Transcription Factor-3 - genetics; Oligonucleotide Array Sequence Analysis; Oocytes - growth & development; Oocytes - metabolism; Physiological aspects
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/1471-2164-12-345

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. 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. 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.