ArticleStem cells (Dayton, Ohio)2014
HIF1α modulates cell fate reprogramming through early glycolytic shift and upregulation of PDK1-3 and PKM2.
Article in Stem cells (Dayton, Ohio), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers, 3 of them syntheses that pooled it.
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Who cites it
151 citing papers in PubMed, 3 syntheses or guidelines pooled it, 251 citations in OpenAlex.
- Pluripotent stem cells: induction and self-renewal.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Pooled it
- Prognostic significance of metabolic enzyme pyruvate kinase M2 in breast cancer: A meta-analysis.Medicine · 2017Pooled it
- Metabolic control of primed human pluripotent stem cell fate and function by the miR-200c-SIRT2 axis.Nature cell biology · 2017Pooled it
- Article
- Induced pluripotent stem cells from a transgenic minipig model of Huntington's disease reveal early metabolic changes.Disease models & mechanisms · 2026Article
- Human iPSC-derived and conventional cancer models in precision oncology: advancing patient-specific therapies from bench to bedside.Journal of experimental & clinical cancer research : CR · 2026Review
- The Regulatory Role of mCells · 2026Review
- The Warburg Effect and Aerobic Glycolysis in Tumors.Cancer treatment and research · 2026Review
- VHL Gene Restoration Supports RCC Reprogramming to iPSCs but Does Not Ensure Line Stability.Cancers · 2025Article
- Neuronal branching in stem cell models of mitochondrial and neurological diseases.Stem cells (Dayton, Ohio) · 2025Review
- Tfcp2l1 as a central integrator of hypoxia, dedifferentiation, and tumor progression.Journal of experimental & clinical cancer research : CR · 2025Review
- Changes in mitochondrial thymidine metabolism and mtDNA copy number during induced pluripotency.Experimental & molecular medicine · 2025Article
- Coupling of stemness maintenance with cell cycle control in stem cells.Frontiers in cell and developmental biology · 2025Review
- RNA-Mediated Regulation of Glycolysis in Embryonic Stem Cell Pluripotency and Differentiation.Current stem cell reports · 2024Article
- Reducing Oxidative Stress and Inflammation by Pyruvate Dehydrogenase Kinase 4 Inhibition Is Important in Prevention of Renal Ischemia-Reperfusion Injury in Diabetic Mice.Diabetes & metabolism journal · 2024Article
- Treatment of Donor Cells with Oxidative Phosphorylation Inhibitor CPI Enhances Porcine Cloned Embryo Development.Animals : an open access journal from MDPI · 2024Article
- ERK/PKM2 Is Mediated in the Warburg Effect and Cell Proliferation in Arsenic-Induced Human L-02 Hepatocytes.Biological trace element research · 2024Article
- Activation of GPR3-β-arrestin2-PKM2 pathway in Kupffer cells stimulates glycolysis and inhibits obesity and liver pathogenesis.Nature communications · 2024Article
- Influences on the Hematopoietic Stem Cell Niche.SciBase hematology & blood disorders · 2024Article
- Unraveling the 2,3-diketo-L-gulonic acid-dependent and -independent impacts of L-ascorbic acid on somatic cell reprogramming.Cell & bioscience · 2023Article
91 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Reprogramming somatic cells to a pluripotent state drastically reconfigures the cellular anabolic requirements, thus potentially inducing cancer-like metabolic transformation. Accordingly, we and others previously showed that somatic mitochondria and bioenergetics are extensively remodeled upon derivation of induced pluripotent stem cells (iPSCs), as the cells transit from oxidative to glycolytic metabolism. In the attempt to identify possible regulatory mechanisms underlying this metabolic restructuring, we investigated the contributing role of hypoxia-inducible factor one alpha (HIF1α), a master regulator of energy metabolism, in the induction and maintenance of pluripotency. We discovered that the ablation of HIF1α function in dermal fibroblasts dramatically hampers reprogramming efficiency, while small molecule-based activation of HIF1α significantly improves cell fate conversion. Transcriptional and bioenergetic analysis during reprogramming initiation indicated that the transduction of the four factors is sufficient to upregulate the HIF1α target pyruvate dehydrogenase kinase (PDK) one and set in motion the glycolytic shift. However, additional HIF1α activation appears critical in the early upregulation of other HIF1α-associated metabolic regulators, including PDK3 and pyruvate kinase (PK) isoform M2 (PKM2), resulting in increased glycolysis and enhanced reprogramming. Accordingly, elevated levels of PDK1, PDK3, and PKM2 and reduced PK activity could be observed in iPSCs and human embryonic stem cells in the undifferentiated state. Overall, the findings suggest that the early induction of HIF1α targets may be instrumental in iPSC derivation via the activation of a glycolytic program. These findings implicate the HIF1α pathway as an enabling regulator of cellular reprogramming.
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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.