title: Correlations between the levels of Oct4 and Nanog as a signature for naïve pluripotency in mouse embryonic stem cells.
abstract: The pluripotent state is traditionally associated with large absolute levels of certain transcription factors such as Nanog and Oct4. Here, we present experimental observations using quantitative immunofluorescence that pluripotency in mouse embryonic stem cells (mESCs) is established by specific ratios between Oct4 and Nanog. When cells are grown in 2i conditions, they exhibit uniform levels of pluripotency and this is associated with a high correlation between the levels of Oct4 and Nanog in individual cells. The correlation is lost when cells differentiate. Our results suggest that the correlation between these two factors and the distribution of Oct4/Nanog ratios can be used as quantifiers to distinguish between three subpopulations in an mESC culture: pluripotent, lineage-primed, and differentiating cells. When we apply these quantifiers to cells with lower levels of Nanog or mutant for β-Catenin or Tcf3, the results suggest that these cells exhibit higher probability of differentiation.
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge, United Kingdom. silvia.munoz@uv.es
authors.forename: Silvia
authors.initials: S
authors.lastname: Muñoz Descalzo
authors.forename: Pau
authors.initials: P
authors.lastname: Rué
authors.forename: Jordi
authors.initials: J
authors.lastname: Garcia-Ojalvo
authors.forename: Alfonso
authors.initials: A
authors.lastname: Martinez Arias
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D051176:beta Catenin; C495267:CTNNB1 protein, mouse; C475540:Nanog protein, mouse; C494174:Pou5f1 protein, mouse; C075668:Tcf3 protein, mouse