ArticleStem cells (Dayton, Ohio)2012
HIF-2α suppresses p53 to enhance the stemness and regenerative potential of human embryonic stem cells.
Article in Stem cells (Dayton, Ohio), 2012. 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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- Hypoxia-driven mobilization of altruistic cancer stem cells in platinum-treated head and neck cancer.Frontiers in immunology · 2024Article
- Mesenchymal stromal cells in hepatic fibrosis/cirrhosis: from pathogenesis to treatment.Cellular & molecular immunology · 2023Review
- The emerging role of oral microbiota in oral cancer initiation, progression and stemness.Frontiers in immunology · 2023Review
- Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases.Frontiers in pharmacology · 2023Review
- Prolyl Hydroxylase Domain Protein Inhibitor Not Harboring a 2-Oxoglutarate Scaffold Protects against Hypoxic Stress.ACS pharmacology & translational science · 2022Article
- The Role of Nitric Oxide in Stem Cell Biology.Antioxidants (Basel, Switzerland) · 2022Review
- Targeting hypoxia-induced tumor stemness by activating pathogen-induced stem cell niche defense.Frontiers in immunology · 2022Article
- Oxygen-sensing mechanisms in development and tissue repair.Development (Cambridge, England) · 2021Review
- Neuronal deficiency of hypoxia-inducible factor 2α increases hypoxic-ischemic brain injury in neonatal mice.Journal of neuroscience research · 2021Article
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- Programmed cell death in stem cell-based therapy: Mechanisms and clinical applications.World journal of stem cells · 2021Review
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- The Interplay Between Tumor Suppressor p53 and Hypoxia Signaling Pathways in Cancer.Frontiers in cell and developmental biology · 2021Review
- N-(2-mercaptopropionyl)-glycine enhances in vitro pig embryo production and reduces oxidative stress.Scientific reports · 2020Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human embryonic stem cells (hESCs) have been reported to exert cytoprotective activity in the area of tissue injury. However, hypoxia/oxidative stress prevailing in the area of injury could activate p53, leading to death and differentiation of hESCs. Here we report that when exposed to hypoxia/oxidative stress, a small fraction of hESCs, namely the SSEA3+/ABCG2+ fraction undergoes a transient state of reprogramming to a low p53 and high hypoxia inducible factor (HIF)-2α state of transcriptional activity. This state can be sustained for a period of 2 weeks and is associated with enhanced transcriptional activity of Oct-4 and Nanog, concomitant with high teratomagenic potential. Conditioned medium obtained from the post-hypoxia SSEA3+/ABCG2+ hESCs showed cytoprotection both in vitro and in vivo. We termed this phenotype as the "enhanced stemness" state. We then demonstrated that the underlying molecular mechanism of this transient phenotype of enhanced stemness involved high Bcl-2, fibroblast growth factor (FGF)-2, and MDM2 expression and an altered state of the p53/MDM2 oscillation system. Specific silencing of HIF-2α and p53 resisted the reprogramming of SSEA3+/ABCG2+ to the enhanced stemness phenotype. Thus, our studies have uncovered a unique transient reprogramming activity in hESCs, the enhanced stemness reprogramming where a highly cytoprotective and undifferentiated state is achieved by transiently suppressing p53 activity. We suggest that this transient reprogramming is a form of stem cell altruism that benefits the surrounding tissues during the process of tissue regeneration.
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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.