ArticleOncotarget2018
Oxidative stress promotes exit from the stem cell state and spontaneous neuronal differentiation.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 73 citations in OpenAlex.
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- The metabolic profiles of cancer stem cells.Stem cell research & therapy · 2026Review
- The impact and mechanisms of preeclampsia on offspring neurodevelopment.Cell & bioscience · 2026Review
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- Stress-inducible phosphoprotein 1 (STIP1) is a critical stemness regulator in mouse embryonic stem cells and early mammalian development.Communications biology · 2025Article
- β-catenin safeguards cell survival via a transcription-independent mechanism during the induction of primitive streak from hESCs.Cell death discovery · 2025Article
- Combined targeting of PRDX6 and GSTP1 as a potential differentiation strategy for neuroblastoma treatment.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Modeling of cancer stem cells and the tumor microenvironment Via NT2/D1 cells to probe pathology and treatment for cancer and beyond.Discover oncology · 2025Review
- Personalized Stem Cell-Based Regeneration in Spinal Cord Injury Care.International journal of molecular sciences · 2025Review
- Emerging Insights into Brain Inflammation: Stem-Cell-Based Approaches for Regenerative Medicine.International journal of molecular sciences · 2025Review
- Effects of Complex I Inhibition on the Architecture of Neural Rosettes Differentiated from Human-Induced Pluripotent Stem Cells.Stem cells and development · 2025Article
- OCT4 translationally promotes AKT signaling as an RNA-binding protein in stressed pluripotent stem cells.Stem cell research & therapy · 2025Article
- Synergistic Antioxidant Effects of Molecular Hydrogen and Cold Atmospheric Plasma in Enhancing Mesenchymal Stem Cell Therapy.Antioxidants (Basel, Switzerland) · 2024Review
- Antioxidant, neuroprotective, and neuroblastoma cells (SH-SY5Y) differentiation effects of melanins and arginine-modified melanins from Daedaleopsis tricolor and Fomes fomentarius.BMC biotechnology · 2024Article
- Photobiomodulation effects on neuronal transdifferentiation of immortalized adipose-derived mesenchymal stem cells.Lasers in medical science · 2024Article
- Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation of the KAT6A/Nrf2 signalling pathway.Chinese medicine · 2024Article
- Comparison of infant bone marrow- and umbilical cord-derived mesenchymal stem cells in multilineage differentiation.Regenerative therapy · 2024Article
- p66Shc signaling and autophagy impact on C2C12 myoblast differentiation during senescence.Cell death & disease · 2024Article
- Cell lineage-guided mass spectrometry reveals increased energy metabolism and reactive oxygen species in the vertebrate organizer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reactive oxygen species (ROS) play important roles in fundamental cellular processes such as proliferation and survival. Here we investigated the effect of oxidative stress on stem cell maintenance and neuronal differentiation in a human embryonic stem cell (hESC) model, Ntera2 (NT2). CM-H2DCFDA and DHE assays confirmed that the oxidizing agent paraquat could induce a high level of ROS in NT2 cells. Quantitative PCR, Western blotting and immunocytochemistry showed that paraquat-induced oxidative stress suppressed the expression of stemness markers, including NANOG, OCT4 and TDGF1, whereas it enhanced the spontaneous expression of neuronal differentiation markers such as PAX6, NEUROD1, HOXA1, NCAM, GFRA1 and TUJ1. The treated cells even exhibited a strikingly different morphology from control cells, extending out long neurite-like processes. The neurogenic effect of ROS on stem cell behaviour was confirmed by the observations that the expression of neuronal markers in the paraquat-treated cells was suppressed by an antioxidant while further enhanced by knocking down Nrf2, a key transcription factor associated with antioxidant signaling. Lastly, paraquat dose-dependently activated the neurogenic MAPK-ERK1/2, which can be reversed by the MEK1/2 inhibitor SL327. Our study suggests that excessive intracellular ROS can trigger the exit from stem cell state and promote the neuronal differentiation of hESCs, and that MAPK-ERK1/2 signaling may play a proactive role in the ROS-induced neuronal differentiation of hESCs.
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