Loss of the Otx2-Binding Site in the Nanog Promoter Affects the Integrity of Embryonic Stem Cell Subtypes and Specification of Inner Cell Mass-Derived Epiblast

Dario Acampora, Daniela Omodei, Giuseppe Petrosino, Arcomaria Garofalo, Marco Savarese, Vincenzo Nigro, Luca Giovanni Di Giovannantonio, Vincenzo Mercadante, Antonio Simeone

Research output: Contribution to journalArticle

Abstract

Mouse embryonic stem cells (ESCs) and the inner cell mass (ICM)-derived epiblast exhibit naive pluripotency. ESC-derived epiblast stem cells (EpiSCs) and the postimplantation epiblast exhibit primed pluripotency. Although core pluripotency factors are well-characterized, additional regulators, including Otx2, recently have been shown to function during the transition from naive to primed pluripotency. Here we uncover a role for Otx2 in the control of the naive pluripotent state. We analyzed Otx2-binding activity in ESCs and EpiSCs and identified Nanog, Oct4, and Sox2 as direct targets. To unravel the Otx2 transcriptional network, we targeted the strongest Otx2-binding site in the Nanog promoter, finding that this site modulates the size of specific ESC-subtype compartments in cultured cells and promotes Nanog expression in vivo, predisposing ICM differentiation to epiblast. Otx2-mediated Nanog regulation thus contributes to the integrity of the ESC state and cell lineage specification in preimplantation development.

Original languageEnglish
Pages (from-to)2651-2664
Number of pages14
JournalCell Reports
Volume15
Issue number12
DOIs
Publication statusPublished - Jun 21 2016

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Keywords

  • Embryonic stem cells
  • Nanog
  • Otx2
  • Pluripotency
  • Preimplantation epiblast

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Acampora, D., Omodei, D., Petrosino, G., Garofalo, A., Savarese, M., Nigro, V., Di Giovannantonio, L. G., Mercadante, V., & Simeone, A. (2016). Loss of the Otx2-Binding Site in the Nanog Promoter Affects the Integrity of Embryonic Stem Cell Subtypes and Specification of Inner Cell Mass-Derived Epiblast. Cell Reports, 15(12), 2651-2664. https://doi.org/10.1016/j.celrep.2016.05.041