ArticleStem cell research & therapy2018
ERK inhibition promotes neuroectodermal precursor commitment by blocking self-renewal and primitive streak formation of the epiblast.
Article in Stem cell research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Establishment of Human Formative Pluripotent Stem Cell-Like Cells Exhibiting Amniotic Differentiation Potentials.Cell proliferation · 2026Article
- Transient inhibition of MEK/ERK and WNT pathways enhances direct differentiation of primed hPSCs into functional trophoblast stem cells.Cell regeneration (London, England) · 2026Article
- Adjusting PSC culture for neural organoid generation.Stem cell reports · 2026Article
- Article
- Lethal Phenotype-Based Database Screening Identifies Ceramide as a Negative Regulator of Primitive Streak Formation.Stem cells (Dayton, Ohio) · 2023Article
- A guide to ERK dynamics, part 2: downstream decoding.The Biochemical journal · 2023Article
- The functional diversity of the POUV-class proteins across vertebrates.Open biology · 2022Review
- The FOXO signaling axis displays conjoined functions in redox homeostasis and stemness.Free radical biology & medicine · 2021Review
- Formative pluripotent stem cells show features of epiblast cells poised for gastrulation.Cell research · 2021Article
- Nuclear FAM289-Galectin-1 interaction controls FAM289-mediated tumor promotion in malignant glioma.Journal of experimental & clinical cancer research : CR · 2019Article
- Modeling Mammalian Commitment to the Neural Lineage Using Embryos and Embryonic Stem Cells.Frontiers in physiology · 2019Review
- MAPK/ERK and JNK pathways regulate lipid synthesis and cell growth of Chlamydomonas reinhardtii under osmotic stress, respectively.Scientific reports · 2018Article
- Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPluripotent stem cells hold great promise for regenerative medicine. However, before clinical application, reproducible protocols for pluripotent stem cell differentiation should be established. Extracellular signal-regulated protein kinase (ERK) signaling plays a central role for the self-renewal of epiblast stem cells (EpiSCs), but its role for subsequent germ layer differentiation is still ambiguous. We proposed that ERK could modulate differentiation of the epiblast.
methodsPD0325901 was used to inhibit ERK activation during the differentiation of embryonic stem cells and EpiSCs. Immunofluorescence, western blot analysis, real-time PCR and flow cytometry were used to detect germ layer markers and pathway activation.
resultsWe demonstrate that the ERK phosphorylation level is lower in neuroectoderm of mouse E7.5 embryos than that in the primitive streak. ERK inhibition results in neural lineage commitment of epiblast. Mechanistically, PD0325901 abrogates the expression of primitive streak markers by β-catenin retention in the cytoplasm, and inhibits the expression of OCT4 and NANOG during EpiSC differentiation. Thus, EpiSCs differentiate into neuroectodermal lineage efficiently under PD0325901 treatment. These results suggest that neuroectoderm differentiation does not require extrinsic signals, supporting the default differentiation of neural lineage.
conclusionsWe report that a single ERK inhibitor, PD0325901, can specify epiblasts and EpiSCs into neural-like cells, providing an efficient strategy for neural differentiation.
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