ArticleStem cells and development2013
Ethanol alters the balance of Sox2, Oct4, and Nanog expression in distinct subpopulations during differentiation of embryonic stem cells.
Article in Stem cells and development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Impact of Prenatal Alcohol Exposure on the Cerebral Circulation: Potential Implications for Stroke.Advances in experimental medicine and biology · 2026Review
- Harnessing the analog computing power of regulatory networks with the Regulatory Network Machine.iScience · 2025Article
- Effects of alcohol on the transcriptome, methylome and metabolome of in vitro gastrulating human embryonic cells.Disease models & mechanisms · 2025Article
- TSP50 facilitates breast cancer stem cell-like properties maintenance and epithelial-mesenchymal transition via PI3K p110α mediated activation of AKT signaling pathway.Journal of experimental & clinical cancer research : CR · 2024Article
- Ethanol Effects on Early Developmental Stages Studied Using the Zebrafish.Biomedicines · 2022Review
- Review
- Modification of stem cell states by alcohol and acetaldehyde.Chemico-biological interactions · 2020Review
- Murine Models for the Study of Fetal Alcohol Spectrum Disorders: An Overview.Frontiers in pediatrics · 2020Review
- Different Effects of Knockouts in ALDH2 and ACSS2 on Embryonic Stem Cell Differentiation.Alcoholism, clinical and experimental research · 2019Article
- Genome-Wide Transcriptome Landscape of Embryonic Brain-Derived Neural Stem Cells Exposed to Alcohol with Strain-Specific Cross-Examination in BL6 and CD1 Mice.Scientific reports · 2019Article
- Stem cells under the influence of alcohol: effects of ethanol consumption on stem/progenitor cells.Cellular and molecular life sciences : CMLS · 2019Review
- Disconnect between alcohol-induced alterations in chromatin structure and gene transcription in a mouse embryonic stem cell model of exposure.Alcohol (Fayetteville, N.Y.) · 2017Article
- Long-term exposure of MCF-7 breast cancer cells to ethanol stimulates oncogenic features.International journal of oncology · 2017Article
- Effects of Ethanol on Cellular Composition and Network Excitability of Human Pluripotent Stem Cell-Derived Neurons.Alcoholism, clinical and experimental research · 2016Article
- Ethanol-mediated activation of the NLRP3 inflammasome in iPS cells and iPS cells-derived neural progenitor cells.Molecular brain · 2016Article
- Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model.Alcohol (Fayetteville, N.Y.) · 2014Article
- Gene expression signatures affected by alcohol-induced DNA methylomic deregulation in human embryonic stem cells.Stem cell research · 2014Article
- Epigenetic regulation of the neural transcriptome and alcohol interference during development.Frontiers in genetics · 2014Review
- Article
- Ethanol diverts early neuronal differentiation trajectory of embryonic stem cells by disrupting the balance of lineage specifiers.PloS one · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The transcription factors Sox2, Oct4, and Nanog regulate within a narrow dose-range embryonic stem (ES) cell pluripotency and cell lineage commitment. Excess of Oct4 relative to Sox2 guides cells to mesoendoderm (ME), while abundance of Sox2 promotes neuroectoderm (NE) formation. Literature does not address whether ethanol interferes with these regulatory interactions during neural development. We hypothesized that ethanol exposure of ES cells in early differentiation causes an imbalance of Oct4 and Sox2 that diverts cells away from NE to ME lineage, consistent with the teratogenesis effects caused by prenatal alcohol exposure. Mouse ES cells were exposed to ethanol (0, 25, 50, and 100 mM) during retinoic acid (10 nM)-directed differentiation to NE for 0-6 days, and the expression of Sox2, Oct4, and Nanog was measured in single live cells by multiparametric flow cytometry, and the cellular phenotype was characterized by immunocytochemistry. Our data showed an ethanol dose- and time-dependent asymmetric modulation of Oct4 and Sox2 expression, as early as after 2 days of exposure. Single-cell analysis of the correlated expression of Sox2, Oct4, and Nanog revealed that ethanol promoted distinct subpopulations with a high Oct4/Sox2 ratio. Ethanol-exposed cells differentiated to fewer β-III tubulin-immunoreactive cells with an immature neuronal phenotype by 4 days. We interpret these data as suggesting that ethanol diverted cells in early differentiation from the NE fate toward the ME lineage. Our results provide a novel insight into the mode of ethanol action and opportunities for discovery of prenatal biomarkers at early stages.
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