ArticleMolecular neurobiology2016
S6K Promotes Dopaminergic Neuronal Differentiation Through PI3K/Akt/mTOR-Dependent Signaling Pathways in Human Neural Stem Cells.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Neuronal Stem Cell and Drug Interactions: A Systematic Review and Meta-Analysis: Concise Review.Stem cells translational medicine · 2019Pooled it
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- Research progress of neural stem cells as a source of dopaminergic neurons for cell therapy in Parkinson's disease.Molecular biology reports · 2024Review
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- mTOR pathway inhibition alters proliferation as well as differentiation of neural stem cells.Frontiers in cellular neuroscience · 2024Article
- MiR-130a-3p regulates neural stem cell differentiation in vitro by targeting Acsl4.Journal of cellular and molecular medicine · 2022Article
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- Targeted inhibition of STAT3 in neural stem cells promotes neuronal differentiation and functional recovery in rats with spinal cord injury.Experimental and therapeutic medicine · 2021Article
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- Icariside II promotes the differentiation of human amniotic mesenchymal stem cells into dopaminergic neuron-like cells.In vitro cellular & developmental biology. Animal · 2021Article
- LncRNA and mRNA Expression Profiles in Methylprednisolone Stimulated Neural Stem Cells.Frontiers in neuroscience · 2021Article
- Maf1 regulates dendritic morphogenesis and influences learning and memory.Cell death & disease · 2020Article
- mTOR signaling in stem and progenitor cells.Development (Cambridge, England) · 2018Review
- Enamel matrix derivative enhances the proliferation and osteogenic differentiation of human periodontal ligament stem cells on the titanium implant surface.Organogenesis · 2017Article
- Lithium chloride promotes neuronal differentiation of rat neural stem cells and enhances neural regeneration in Parkinson's disease model.Cytotechnology · 2017Article
- Formyl peptide receptors promotes neural differentiation in mouse neural stem cells by ROS generation and regulation of PI3K-AKT signaling.Scientific reports · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has recently been reported that the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway regulates neuronal differentiation of neural stem cells (NSCs) derived from rats or mice and is essential for the self-renewal of human embryonic stem cells (hESCs). However, the roles of PI3K/Akt/mTOR signaling pathways during proliferation and dopaminergic neuronal differentiation of human neural stem cells (hNSCs) are poorly understood. In this study, we examined the effect of regulation of these intracellular signaling pathways in hNSCs on the potential to maintain proliferation and induce dopaminergic neuronal differentiation. Dopaminergic neuronal differentiation depended on the concentration of insulin in our culture system. Inhibition of PI3K/Akt with LY294002 reduced proliferation and inhibited dopaminergic neuronal differentiation of these cells. We also found that rapamycin, a specific inhibitor of mTOR, significantly reduced neuronal differentiation without affecting proliferation. Inhibition of the Akt/mTOR signaling pathway led to inhibition of p70 ribosomal S6 kinase (S6K) signaling, which reduced dopaminergic neuronal differentiation in hNSCs. Inhibition of S6K by a specific chemical inhibitor, PF-4708671 inhibited dopaminergic neuronal differentiation of hNSCs. As expected, transduction with a dominant negative S6K1 (S6K1-DN) construct impaired dopaminergic neuronal differentiation of hNSCs. Conversely, overexpression of constitutively active S6K1 (S6K1-CA) promoted dopaminergic neuronal differentiation of these cells. In a survival study, 4 weeks after transplantation, no or very few donor cells were viable in striata grafted with S6K1-DN-transduced hNSCs. In contrast, S6K1-CA-transduced hNSCs survived, integrated into striata to generate tubular masses of grafts and differentiated toward TH-positive cells. Taken together, these data demonstrated that insulin promotes dopaminergic neuronal differentiation through a PI3K/Akt/mTOR-dependent pathway and that S6K plays a critical role in dopaminergic neuronal differentiation in hNSCs.
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