Gatekeeper of pluripotency: A common Oct4 transcriptional network operates in mouse eggs and embryonic stem cells
1 Sezione di Istologia ed Embriologia, Dipartimento di Medicina Sperimentale, Universita' degli Studi di Parma, Parma, Italy
2 Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy
3 Laboratorio di Biologia dello Sviluppo, Dipartimento di Biologia Animale, Universita' degli Studi di Pavia, Pavia, Italy
4 Centro di Ingegneria Tissutale, Universita' degli Studi di Pavia, Pavia, Italy
5 Dipartimento di Informatica e Sistemistica, Universita' degli Studi di Pavia, Pavia, Italy
6 Molecular Embryology and Aging Group, Department of Vertebrate Genomics. Max-Planck Institute for Molecular Genetics, Berlin, Germany
7 Centro di Eccellenza in Biologia Applicata, Universita' degli Studi di Pavia, Pavia, Italy
BMC Genomics 2011, 12:345 doi:10.1186/1471-2164-12-345Published: 5 July 2011
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.