ArticleCellular and molecular neurobiology2014
Regulatory role of the JNK-STAT1/3 signaling in neuronal differentiation of cultured mouse embryonic stem cells.
Article in Cellular and molecular neurobiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Attenuated innate immunity in embryonic stem cells: mechanisms and therapeutic applications.Cell & bioscience · 2025Review
- Recent research advances in interleukin, microRNA and neuroendocrine tumor biomarkers (Review).Molecular and clinical oncology · 2025Review
- Refate identifies chemical compounds to target trans-regulatory networks for cellular conversion.bioRxiv : the preprint server for biology · 2025Article
- Interplay Between Key Molecular Signaling Pathways and Immune Players Following Brain Irradiation.Mediators of inflammation · 2025Review
- PTPRJ is a negative regulator of insulin signaling in neuronal cells, impacting protein biosynthesis, and neurite outgrowth.Journal of neuroendocrinology · 2024Article
- Small Molecules Temporarily Induce Neuronal Features in Adult Canine Dermal Fibroblasts.International journal of molecular sciences · 2023Article
- Kinase inhibit region of SOCS3 attenuates IL6-induced proliferation and astrocytic differentiation of neural stem cells via cross talk between signaling pathways.CNS neuroscience & therapeutics · 2023Article
- Gastrin: From Physiology to Gastrointestinal Malignancies.Function (Oxford, England) · 2022Review
- Phosphatidylcholine restores neuronal plasticity of neural stem cells under inflammatory stress.Scientific reports · 2021Article
- Genome analysis identifies differences in the transcriptional targets of duodenal versus pancreatic neuroendocrine tumours.BMJ open gastroenterology · 2021Article
- Article
- FOXC1 Downregulates Nanog Expression by Recruiting HDAC2 to Its Promoter in F9 Cells Treated by Retinoic Acid.International journal of molecular sciences · 2021Article
- Pim-1 Protects Retinal Ganglion Cells by Enhancing Their Regenerative Ability Following Optic Nerve Crush.Experimental neurobiology · 2020Article
- JNK Signaling in Stem Cell Self-Renewal and Differentiation.International journal of molecular sciences · 2020Review
- A New Method for Chromosomes Preparation by ATP-Competitive Inhibitor SP600125Frontiers in bioengineering and biotechnology · 2020Article
- Modulation of Stem Cells as Therapeutics for Severe Mental Disorders and Cognitive Impairments.Frontiers in psychiatry · 2020Review
- Antitumor activity of Raddeanin A is mediated by Jun amino-terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma.Cancer science · 2019Article
- Retinoic Acid Induces Differentiation of Mouse F9 Embryonic Carcinoma Cell by Modulating the miR-485 Targeting of Abhd2.International journal of molecular sciences · 2019Article
- Priming of the Cells: Hypoxic Preconditioning for Stem Cell Therapy.Chinese medical journal · 2017Review
- ERK signaling is required for VEGF-A/VEGFR2-induced differentiation of porcine adipose-derived mesenchymal stem cells into endothelial cells.Stem cell research & therapy · 2017Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Stem cell transplantation therapy has provided promising hope for the treatment of a variety of neurodegenerative disorders. Among challenges in developing disease-specific stem cell therapies, identification of key regulatory signals for neuronal differentiation is an essential and critical issue that remains to be resolved. Several lines of evidence suggest that JNK, also known as SAPK, is involved in neuronal differentiation and neural plasticity. It may also play a role in neurite outgrowth during neuronal development. In cultured mouse embryonic stem (ES) cells, we test the hypothesis that the JNK pathway is required for neuronal differentiation. After neural induction, the cells were plated and underwent differentiation for up to 5 days. Western blot analysis showed a dramatic increase in phosphorylated JNKs at 1-5 days after plating. The phosphorylation of JNK subsequently induced activation of STAT1 and STAT3 that lead to expressions of GAP-43, neurofilament, βIII-tubulin, and synaptophysin. NeuN-colabelled with DCX, a marker for neuroblast, was enhanced by JNK signaling. Neuronal differentiation of ES cells was attenuated by treatment with SP600125, which inhibited the JNK activation and decreased the activation of STAT1 and STAT3, and consequently suppressed the expressions of GAP-43, neurofilament, βIII-tubulin, and the secretion of VEGF. Data from immunocytochemistry indicated that the nuclear translocation of STAT3 was reduced, and neurites of ES-derived neurons were shorter after treatment with SP600125 compared with control cells. These results suggest that the JNK-STAT3 pathway is a key regulator required for early neuronal differentiation of mouse ES cells. Further investigation on expression of JNK isoforms showed that JNK-3 was significantly upregulated during the differentiation stage, while JNK-1 and JNK-2 levels decreased. Our study provided interesting information on JNK functions during ES cell neuronal differentiation.
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