ArticleNature2017
Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 1 of them a synthesis that pooled it.
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Who cites it
173 citing papers in PubMed, 1 synthesis or guideline pooled it, 290 citations in OpenAlex.
- Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells.Stem cell research & therapy · 2022Pooled it
- Overconfluent culture promotes cell cycle synchronization in mouse embryonic stem cells for efficient cloned embryo production.The Journal of reproduction and development · 2026Article
- Dnmt3L Acetylation as a Post-Translational Switch Linking Extracellular Environment to Epigenetic Stability in Pluripotent Stem Cells.Stem cell reviews and reports · 2026Article
- A panel of Diversity Outbred mouse embryonic stem cells: enabling the functional characterization of natural genetic variationbioRxiv : the preprint server for biology · 2026Article
- The making of cells and organs in xenogeneic animal bioreactor.Signal transduction and targeted therapy · 2026Review
- Epigenetic blind spots - the role of DNA methylation dynamics in stem cell-based models of embryogenesis.FEBS letters · 2026Article
- PCBP1 orchestrates amino acid metabolism burst during the naïve-to-primed pluripotency transition.Stem cell reports · 2026Article
- Chromosome X dosage modulates development of aneuploidy in genetically diverse mouse embryonic stem cells.Stem cell reports · 2026Article
- Rat cell-derived kidney generation via interspecies blastocyst complementation in an Osr1-KO mouse model.Stem cell reports · 2026Article
- Mechanisms coordinating exit from the stem cell state in mammals.Genes & development · 2026Review
- Mitochondrial NADH-redox inflexibility constrains genomic and epigenetic stability in pluripotent stem cells.The EMBO journal · 2026Article
- Naïve pluripotency and genomic stability are coordinated in embryonic stem cells by a novel pluripotency regulator ZFP998.Nucleic acids research · 2026Article
- Constitutive EGFR Activation Induced by PTPRR Downregulation Confers Resistance to KRAS Inhibitors.Cancer research communications · 2026Article
- Uncovering the acetylation sites of Dnmt3L that regulate protein stability and differentiation potency in embryonic stem cells.Experimental & molecular medicine · 2026Article
- African pygmy mouse iPSCs as a model for in vitro embryogenesis, interspecies chimerism, and blastocyst complementation.Cell reports methods · 2026Article
- ERK phosphorylates HNRNPF to promote the proliferation and suppress the differentiation of embryonic stem cells.Nucleic acids research · 2026Article
- Genetic and chromatin regulation of Pvt1 monoallelic expression.Cell reports · 2025Article
- Optimized derivation and culture system of human naïve pluripotent stem cells with enhanced DNA methylation status and genomic stability.Protein & cell · 2025Article
- Article
- Cdh2, a downstream target of Hes7, regulates somitogenesis by supporting FGF signalling.Development (Cambridge, England) · 2025Article
113 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 7 institutions in 3 countries.
Funding
Abstract
Concomitant activation of the Wnt pathway and suppression of Mapk signalling by two small molecule inhibitors (2i) in the presence of leukaemia inhibitory factor (LIF) (hereafter termed 2i/L) induces a naive state in mouse embryonic stem (ES) cells that resembles the inner cell mass (ICM) of the pre-implantation embryo. Since the ICM exists only transiently in vivo, it remains unclear how sustained propagation of naive ES cells in vitro affects their stability and functionality. Here we show that prolonged culture of male mouse ES cells in 2i/L results in irreversible epigenetic and genomic changes that impair their developmental potential. Furthermore, we find that female ES cells cultured in conventional serum plus LIF medium phenocopy male ES cells cultured in 2i/L. Mechanistically, we demonstrate that the inhibition of Mek1/2 is predominantly responsible for these effects, in part through the downregulation of DNA methyltransferases and their cofactors. Finally, we show that replacement of the Mek1/2 inhibitor with a Src inhibitor preserves the epigenetic and genomic integrity as well as the developmental potential of ES cells. Taken together, our data suggest that, although short-term suppression of Mek1/2 in ES cells helps to maintain an ICM-like epigenetic state, prolonged suppression results in irreversible changes that compromise their developmental potential.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.