ArticleStem cells and development2012
Exacerbation of oxidative stress-induced cell death and differentiation in induced pluripotent stem cells lacking heme oxygenase-1.
Article in Stem cells and development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 57 citations in OpenAlex.
- Impact of CD34European journal of haematology · 2026Article
- Human pluripotent stem cell-derived hepatic progenitors exhibit a partially hypoimmunogenic phenotype and actively inhibit immune responses.Frontiers in immunology · 2025Article
- Role of NF-κB signaling pathway in HIn vitro cellular & developmental biology. Animal · 2024Article
- Mechanism of Action and Therapeutic Implications of Nrf2/HO-1 in Inflammatory Bowel Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Characterization of mitochondrial and metabolic alterations induced by trisomy 21 during neural differentiation.Free radical biology & medicine · 2023Article
- The effects of continuous exposure to low-dose chlorine dioxide gas on the characteristics of induced pluripotent stem cells.Regenerative therapy · 2022Article
- Article
- High dose expression of heme oxigenase-1 induces retinal degeneration through ER stress-related DDIT3.Molecular neurodegeneration · 2021Article
- Role of Heme-Oxygenase-1 in Biology of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells.Cells · 2021Article
- Article
- The Dynamic Proteome of Oligodendrocyte Lineage Differentiation Features Planar Cell Polarity and Macroautophagy Pathways.GigaScience · 2020Article
- Tissue engineering strategies combining molecular targets against inflammation and fibrosis, and umbilical cord blood stem cells to improve hampered muscle and skin regeneration following cleft repair.Medicinal research reviews · 2020Review
- Modelling heme-mediated brain injury associated with cerebral malaria in human brain cortical organoids.Scientific reports · 2019Article
- Endodermal differentiation of human induced pluripotent stem cells using simple dialysis culture system in suspension culture.Regenerative therapy · 2019Article
- Murine Bone Marrow Mesenchymal Stromal Cells Respond Efficiently to Oxidative Stress Despite the Low Level of Heme Oxygenases 1 and 2.Antioxidants & redox signaling · 2018Article
- Loss of heme oxygenase-1 accelerates mesodermal gene expressions during embryoid body development from mouse embryonic stem cells.Redox biology · 2018Article
- Heme Oxygenases in Cardiovascular Health and Disease.Physiological reviews · 2016Review
- Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism.Cellular and molecular life sciences : CMLS · 2016Review
- Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4.Cell reports · 2016Article
- Hypoxia-Induced Epithelial-Mesenchymal Transition Is Involved in Bleomycin-Induced Lung Fibrosis.BioMed research international · 2015Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Embryonic stem cells (ESCs) are promising donor sources in cell therapies for various diseases. Although low levels of reactive oxygen species (ROS) are necessary for the maintenance of stem cells, increased ROS levels initiate differentiation and cell damage. We and others have previously demonstrated that heme oxygenase (HO)-1, a stress response protein with antioxidative and anti-inflammatory properties, plays critical protective functions in cardiovascular and other diseases. However, the functions of HO-1 in ESCs remain to be elucidated. Our goal was to investigate the roles of HO-1 in ESC survival and differentiation. Due to the lack of HO-1-deficient ESCs, we used Oct3/4, Sox2, c-Myc, and Klf4 retroviruses to reprogram mouse embryonic fibroblasts into induced pluripotent stem (iPS) cells of different HO-1 genotypes. These iPS-HO-1 cells exhibited characteristics of mouse ESCs (mESCs) and formed teratomas that were composed of cell types of all 3 germ layers after injected into severe combined immunodeficiency mice. In response to oxidant stress, iPS-HO-1(-/-) cells accumulated higher levels of intracellular ROS compared with D3 mESCs or iPS-HO-1(+/+) cells and were more prone to oxidant-induced cell death. Spontaneous differentiation experiments revealed that Oct4 levels were significantly lower in iPS-HO-1(-/-) cells after leukemia inhibitory factor withdrawal and removal of feeders. Further, during the course of spontaneous differentiation, iPS-HO-1(-/-) cells had enhanced Erk1/2 phosphorylation, which has been linked to ESC differentiation. By the loss-of-function approach using iPS-HO-1(-/-) cells, our results demonstrate that a lack of HO-1 renders iPS cells more prone to oxidative stress-induced cell death and differentiation.
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