ArticleStem cells and development2014
Role of notch signaling in the maintenance of human mesenchymal stem cells under hypoxic conditions.
Article in Stem cells and development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- Notch signaling regulates the secretion of pro-metastatic factors in extracellular vesicles in liposarcoma.Cancer letters · 2026Article
- Aberrant EZHIP expression drives tumorigenesis in osteosarcoma.Nature communications · 2025Article
- From Quiescence to Activation: The Reciprocal Regulation of Ras and Rho Signaling in Hepatic Stellate Cells.Cells · 2025Article
- Glycolysis modulation: New therapeutic strategies to improve pulmonary hypertension (Review).International journal of molecular medicine · 2024Review
- [Role of Notch 1 signaling and glycolysis in the pathogenic mechanism of adenomyosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Notch mediates the glycolytic switch via PI3K/Akt signaling to support embryonic development.Cellular & molecular biology letters · 2023Article
- Notch signaling, hypoxia, and cancer.Frontiers in oncology · 2023Review
- [Hypoxia promotes differentiation of human induced pluripotent stem cells into embryoid bodiesNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Hypoxia Regulates the Self-Renewal of Endometrial Mesenchymal Stromal/Stem-like Cells via Notch Signaling.International journal of molecular sciences · 2022Article
- Adipose-derived stromal/stem cells improve epidermal homeostasis.Scientific reports · 2019Article
- Mathematical modelling of interacting mechanisms for hypoxia mediated cell cycle commitment for mesenchymal stromal cells.BMC systems biology · 2018Article
- Mash1-dependent Notch Signaling Pathway Regulates GABAergic Neuron-Like Differentiation from Bone Marrow-Derived Mesenchymal Stem Cells.Aging and disease · 2017Article
- Eat, breathe, ROS: controlling stem cell fate through metabolism.Expert review of cardiovascular therapy · 2017Review
- [Effect of miR- 155 on immune- factors and its mechanism in mesenchymal stem cells under hypoxic environment].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2016Article
- Notch signaling represses hypoxia-inducible factor-1α-induced activation of Wnt/β-catenin signaling in osteoblasts under cobalt-mimicked hypoxia.Molecular medicine reports · 2016Article
- Low Oxygen Modulates Multiple Signaling Pathways, Increasing Self-Renewal, While Decreasing Differentiation, Senescence, and Apoptosis in Stromal MIAMI Cells.Stem cells and development · 2016Article
- Targeting Notch to overcome radiation resistance.Oncotarget · 2016Review
- Hypoxia Inhibits De Novo Vascular Assembly of Adipose-Derived Stromal/Stem Cell Populations, but Promotes Growth of Preformed Vessels.Tissue engineering. Part A · 2016Article
- Involvement of Notch1/Hes signaling pathway in ankylosing spondylitis.International journal of clinical and experimental pathology · 2015Article
- Hypoxia-cultured human adipose-derived mesenchymal stem cells are non-oncogenic and have enhanced viability, motility, and tropism to brain cancer.Cell death & disease · 2014Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human adipose tissue-derived multilineage progenitor cells (hADMPCs) are attractive for cell therapy and tissue engineering because of their multipotency and ease of isolation without serial ethical issues. However, their limited in vitro lifespan in culture systems hinders their therapeutic application. Some somatic stem cells, including hADMPCs, are known to be localized in hypoxic regions; thus, hypoxia may be beneficial for ex vivo culture of these stem cells. These cells exhibit a high level of glycolytic metabolism in the presence of high oxygen levels and further increase their glycolysis rate under hypoxia. However, the physiological role of glycolytic activation and its regulatory mechanisms are still incompletely understood. Here, we show that Notch signaling is required for glycolysis regulation under hypoxic conditions. Our results demonstrate that 5% O2 dramatically increased the glycolysis rate, improved the proliferation efficiency, prevented senescence, and maintained the multipotency of hADMPCs. Intriguingly, these effects were not mediated by hypoxia-inducible factor (HIF), but rather by the Notch signaling pathway. Five percent O2 significantly increased the level of activated Notch1 and expression of its downstream gene, HES1. Furthermore, 5% O2 markedly increased glucose consumption and lactate production of hADMPCs, which decreased back to normoxic levels on treatment with a γ-secretase inhibitor. We also found that HES1 was involved in induction of GLUT3, TPI, and PGK1 in addition to reduction of TIGAR and SCO2 expression. These results clearly suggest that Notch signaling regulates glycolysis under hypoxic conditions and, thus, likely affects the cell lifespan via glycolysis.
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Registered trials
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.