ArticleEMBO molecular medicine2012
Hypoxic priming of mESCs accelerates vascular-lineage differentiation through HIF1-mediated inverse regulation of Oct4 and VEGF.
Article in EMBO molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- A Mechanistic Model of the HIF-1/HIF-2 Switch Regulating Hypoxia-Induced Cancer Stemness.International journal of molecular sciences · 2026Article
- From molecular damage to regulatory constraint: epigenetic and metabolic limits of cellular plasticity in aging.Frontiers in aging · 2026Review
- Human bone marrow-mesenchymal stem cells differentiation into brain-like endothelial cells.Turkish journal of biology = Turk biyoloji dergisi · 2026Article
- Current perspectives on regenerative potential of mesenchymal stem cells in alleviating cardiac injuries: Molecular pathways and therapeutic enhancement.World journal of stem cells · 2025Review
- Purple Potato Extract Suppresses Hypoxia-Induced Metabolic Reprogramming and Inhibits HIF-1α Signaling in Caco-2 Cells.Nutrients · 2025Article
- Redox heterogeneity in mouse embryonic stem cells individualizes cell fate decisions.Developmental cell · 2024Article
- Uncovering the role of TET2-mediated ENPEP activation in trophoblast cell fate determination.Cellular and molecular life sciences : CMLS · 2024Article
- The Progress in Molecular Transport and Therapeutic Development in Human Blood-Brain Barrier Models in Neurological Disorders.Cellular and molecular neurobiology · 2024Review
- Effect and mechanism of hypoxia on differentiation of porcine-induced pluripotent stem cells into vascular endothelial cells.In vitro cellular & developmental biology. Animal · 2024Article
- Article
- Regulation of Embryonic Stem Cell Self-Renewal.Life (Basel, Switzerland) · 2022Review
- Response of Pluripotent Stem Cells to Environmental Stress and Its Application for Directed Differentiation.Biology · 2021Review
- Hypoxia as a Driving Force of Pluripotent Stem Cell Reprogramming and Differentiation to Endothelial Cells.Biomolecules · 2020Review
- Hypoxia induces an endometrial cancer stem-like cell phenotype via HIF-dependent demethylation of SOX2 mRNA.Oncogenesis · 2020Article
- The Redox Theory of Development.Antioxidants & redox signaling · 2020Review
- The MicroRNA-92a/Sp1/MyoD Axis Regulates Hypoxic Stimulation of Myogenic Lineage Differentiation in Mouse Embryonic Stem Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Lung Microvascular Niche, Repair, and Engineering.Frontiers in bioengineering and biotechnology · 2020Review
- Adipose tissue loss and lipodystrophy in xylosyltransferase II deficient mice.International journal of obesity (2005) · 2019Article
- Strategies for derivation of endothelial lineages from human stem cells.Stem cell research & therapy · 2019Review
- Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies.Nature communications · 2019Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxic microenvironment plays an important role in determining stem cell fates. However, it is controversial to which direction between self-renewal and differentiation the hypoxia drives the stem cells. Here, we investigated whether a short exposure to hypoxia (termed 'hypoxic-priming') efficiently directed and promoted mouse embryonic stem cells (mESCs) to differentiate into vascular-lineage. During spontaneous differentiation of embryoid bodies (EBs), hypoxic region was observed inside EB spheroids even under normoxic conditions. Indeed, hypoxia-primed EBs more efficiently differentiated into cells of vascular-lineage, than normoxic EBs did. We found that hypoxia suppressed Oct4 expression via direct binding of HIF-1 to reverse hypoxia-responsive elements (rHREs) in the Oct4 promoter. Furthermore, vascular endothelial growth factor (VEGF) was highly upregulated in hypoxia-primed EBs, which differentiated towards endothelial cells in the absence of exogenous VEGF. Interestingly, this differentiation was abolished by the HIF-1 or VEGF blocking. In vivo transplantation of hypoxia-primed EBs into mice ischemic limb elicited enhanced vessel differentiation. Collectively, our findings identify that hypoxia enhanced ESC differentiation by HIF-1-mediated inverse regulation of Oct4 and VEGF, which is a novel pathway to promote vascular-lineage differentiation.
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Registered trials
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