Transient Downregulation of Nanog and Oct4 Induced by DETA/NO Exposure in Mouse Embryonic Stem Cells Leads to

Sergio Mora-Castilla1, Juan R Tejedo2, Rafael Tapia-Limonchi2

  • 1Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University Pablo de Olavide, Biomedical Research Network (CIBER) of Diabetes and Related Metabolic Diseases, Red-Tercel, Avenida Américo Vespucio S/N, 41092 Seville, Spain ; Sanford Consortium for Regenerative Medicine, University of California San Diego, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.

Stem Cells International
|December 30, 2014
PubMed

Insights

Pluripotency genes Nanog and Oct4 reexpressed in mouse embryonic stem cells during differentiation. Nanog reexpression influences endoderm marker expression and disrupts mesendoderm transition.

Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Epigenetics

Background:

  • Pluripotency genes maintain embryonic stem cell identity.
  • Their role during differentiation is not fully understood.
  • Investigating pluripotency gene regulation offers insights into developmental processes.

Purpose of the Study:

  • To investigate the role of Nanog and Oct4 in mouse embryonic stem cell (mESC) differentiation.
  • To explore the regulatory mechanisms behind Nanog reexpression.
  • To understand how Nanog affects lineage specification during differentiation.

Main Methods:

  • Used two mouse embryonic stem cell (mESC) lines.
  • Induced differentiation using DETA/NO.
  • Performed confocal analysis to examine gene expression.
  • Assessed histone modifications at gene promoters.

Main Results:

  • Nanog and Oct4 were reexpressed in mESCs upon DETA/NO treatment.
  • Cells expressed both endoderm (Gata4, FoxA2) and mesoderm (Flk1, Mef2c) markers.
  • Nanog reexpression correlated with endoderm marker expression.
  • Acetylated histone H3 at the Nanog promoter was involved in its reexpression.
  • Nanog repressed Brachyury, disrupting mesendoderm transition.

Conclusions:

  • Nanog and Oct4 reexpression occurs during mESC differentiation.
  • Nanog plays a role in endoderm specification and mesendoderm transition.
  • Histone acetylation is implicated in Nanog reexpression.
  • This study reveals a complex regulatory role for pluripotency factors during differentiation.