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.

Highlights

  • Oct4 is a key factor of an expanded transcriptional network (Oct4-transcriptional networks (TN)) that governs pluripotency and self-renewal in embryonic stem cells (ESCs) and in the inner cell mass from which ESCs are derived

  • Using the Gene Ontology (GO) enrichment analysis tool provided by the data mining and bioinformatics software Orange http://www.ailab.si/ orange, 3102 (Additional file 1) out of 8354 regulated genes were assigned to seven major biological processes (Figure 1A), including development, cellular and macromolecule localisation, apoptosis, transcription, intracellular signalling, cell cycle and translation

  • Numerous genes of the maternal Oct4 transcriptional network are known members of the Oct4 interactome in ESCs Using the Network Explorer module provided by the Orange software, we explored public databases for links between the group of 32 OCT4-regulated genes used as bait, and all the annotated mouse gene sequences

Read more

Summary

Introduction

Oct 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 question that remains unanswered is concerned with the nature of the transcriptional networks (TN) in which maternal-effect genes operate This knowledge would further our understanding of the molecular identity of a developmentally competent egg (metaphase II, MII, oocyte) and would allow to investigate how this identity is modified during the switch to an embryonic control of development. Most of our knowledge on Oct functions comes from studies that describe its key role in the control of transcriptional regulatory circuits that maintain pluripotency in the inner cell mass (ICM) of the blastocyst [4] and in embryonic stem cells (ESCs) [5,6,7,8,9,10]. OCT4 is recognised for its capacity, when ectopically expressed in combination with other transcription factors (i.e., NANOG, SOX2, cMYC, KLF4 or ESRRB), to reprogram differentiated cells into pluripotent cells (induced pluripotent stem cells, iPS cells) [11,12,13,14,15]

Objectives
Methods
Results
Discussion
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.