ArticlePloS one2011
Molecular insights into reprogramming-initiation events mediated by the OSKM gene regulatory network.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Pluripotent stem cells: induction and self-renewal.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Pooled it
- Conserved Partial Reprogramming Effects on the Methylome.Epigenomes · 2026Article
- Gene therapy for hearing loss: challenges and the promise of cellular plasticity and epigenetic modulation.Frontiers in neurology · 2024Article
- Initiation phase cellular reprogramming ameliorates DNA damage in the ERCC1 mouse model of premature aging.Frontiers in aging · 2023Article
- Quantitative analysis of mitochondrial morphologies in human induced pluripotent stem cells for Leigh syndrome.Stem cell research · 2021Article
- Strategies for controlling the innate immune activity of conventional and self-amplifying mRNA therapeutics: Getting the message across.Advanced drug delivery reviews · 2021Review
- Production of viable chicken by allogeneic transplantation of primordial germ cells induced from somatic cells.Nature communications · 2021Article
- A PIANO (Proper, Insufficient, Aberrant, and NO Reprogramming) Response to the Yamanaka Factors in the Initial Stages of Human iPSC Reprogramming.International journal of molecular sciences · 2020Article
- Heterochromatin loosening by the Oct4 linker region facilitates Klf4 binding and iPSC reprogramming.The EMBO journal · 2020Article
- Energy Metabolism Regulates Stem Cell Pluripotency.Frontiers in cell and developmental biology · 2020Review
- Human-stimulated oocyte extract induces genetic and mitochondrial reprogramming of mesenchymal stromal cells.PloS one · 2020Article
- Episomal Induced Pluripotent Stem Cells: Functional and Potential Therapeutic Applications.Cell transplantation · 2019Review
- Chemical suppression of specific C-C chemokine signaling pathways enhances cardiac reprogramming.The Journal of biological chemistry · 2019Article
- Mechanisms of the Metabolic Shift during Somatic Cell Reprogramming.International journal of molecular sciences · 2019Review
- Endothelial Differentiation G Protein-Coupled Receptor 5 Plays an Important Role in Induction and Maintenance of Pluripotency.Stem cells (Dayton, Ohio) · 2019Article
- Peroxisome Proliferator-Activated Receptor α Agonist and Its Target Nanog Cooperate to Induce Pluripotency.Journal of clinical medicine · 2018Article
- Effects of the Extracts from Fruit and Stem ofJournal of clinical medicine · 2018Article
- Transflammation: How Innate Immune Activation and Free Radicals Drive Nuclear Reprogramming.Antioxidants & redox signaling · 2018Review
- Pharmacological Regulation of Oxidative Stress in Stem Cells.Oxidative medicine and cellular longevity · 2018Review
- miR-524-5p of the primate-specific C19MC miRNA cluster targets TP53IPN1- and EMT-associated genes to regulate cellular reprogramming.Stem cell research & therapy · 2017Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Somatic cells can be reprogrammed to induced pluripotent stem cells by over-expression of OCT4, SOX2, KLF4 and c-MYC (OSKM). With the aim of unveiling the early mechanisms underlying the induction of pluripotency, we have analyzed transcriptional profiles at 24, 48 and 72 hours post-transduction of OSKM into human foreskin fibroblasts. Experiments confirmed that upon viral transduction, the immediate response is innate immunity, which induces free radical generation, oxidative DNA damage, p53 activation, senescence, and apoptosis, ultimately leading to a reduction in the reprogramming efficiency. Conversely, nucleofection of OSKM plasmids does not elicit the same cellular stress, suggesting viral response as an early reprogramming roadblock. Additional initiation events include the activation of surface markers associated with pluripotency and the suppression of epithelial-to-mesenchymal transition. Furthermore, reconstruction of an OSKM interaction network highlights intermediate path nodes as candidates for improvement intervention. Overall, the results suggest three strategies to improve reprogramming efficiency employing: 1) anti-inflammatory modulation of innate immune response, 2) pre-selection of cells expressing pluripotency-associated surface antigens, 3) activation of specific interaction paths that amplify the pluripotency signal.
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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.