ArticleStem cells and development2015
Hypoxia enhances differentiation of mouse embryonic stem cells into definitive endoderm and distal lung cells.
Article in Stem cells and development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 66 citations in OpenAlex.
- Glioblastoma Stem Cells and Tumour Microenvironment: Interactions Across Hypoxia, Vasculature and Immune Modulation.International journal of molecular sciences · 2026Review
- SOX17 in pulmonary arterial hypertension: from development to clinical phenotype.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- PHD2 safeguards modest mesendoderm development.Communications biology · 2024Article
- Data integration and inference of gene regulation using single-cell temporal multimodal data with scTIE.Genome research · 2024Article
- STAT3 and HIF1α cooperatively mediate the transcriptional and physiological responses to hypoxia.Cell death discovery · 2023Article
- scTIE: data integration and inference of gene regulation using single-cell temporal multimodal data.bioRxiv : the preprint server for biology · 2023Article
- Alginate Beads as a Promising Tool for Successful Production of Viable and Pluripotent Human-Induced Pluripotent Stem Cells in a 3D Culture System.Stem cells and cloning : advances and applications · 2023Article
- Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids.Development (Cambridge, England) · 2022Article
- Hypoxia is fine-tuned by Hif-1α and regulates mesendoderm differentiation through the Wnt/β-Catenin pathway.BMC biology · 2022Article
- Integrating Oxygen and 3D Cell Culture System: A Simple Tool to Elucidate the Cell Fate Decision of hiPSCs.International journal of molecular sciences · 2022Article
- Article
- Oxidative stress induced by NOX2 contributes to neuropathic pain via plasma membrane translocation of PKCε in rat dorsal root ganglion neurons.Journal of neuroinflammation · 2021Article
- Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration.Stem cell research & therapy · 2020Article
- In Vitro Induction of Pluripotency from Equine Fibroblasts in 20% or 5% Oxygen.Stem cells international · 2020Article
- Metabolism in pluripotency: Both driver and passenger?The Journal of biological chemistry · 2019Review
- Physiological oxygen tension reduces hepatocyte dedifferentiation in in vitro culture.Scientific reports · 2017Article
- Effect of Hypoxia on Self-Renewal Capacity and Differentiation in Human Tendon-Derived Stem Cells.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Effect of Hypoxia on the Differentiation and the Self-Renewal of Metanephrogenic Mesenchymal Stem Cells.Stem cells international · 2017Article
- Pluripotent Stem Cell Metabolism and Mitochondria: Beyond ATP.Stem cells international · 2017Review
- Lung bioengineering: physical stimuli and stem/progenitor cell biology interplay towards biofabricating a functional organ.Respiratory research · 2016Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
We investigated the effects of hypoxia on spontaneous (SP)- and activin A (AA)-induced definitive endoderm (DE) differentiation of mouse embryonic stem cells (mESCs) and their subsequent differentiation into distal pulmonary epithelial cells. SP differentiation for 6 days of mESCs toward endoderm at hypoxia of 1% O2, but not at 3% or 21% (normoxia), increased the expression of Sox17 and Foxa2 by 31- and 63-fold above maintenance culture, respectively. Treatment of mESCs with 20 ng/mL AA for 6 days under hypoxia further increased the expression of DE marker genes Sox17, Foxa2, and Cxcr4 by 501-, 1,483-, and 126-fold above maintenance cultures, respectively. Transient exposure to hypoxia, as short as 24 h, was sufficient to enhance AA-induced endoderm formation. The involvement of hypoxia-inducible factor (HIF)-1α and reactive oxygen species (ROS) in the AA-induced endoderm enrichment was assessed using HIF-1α(-/-) mESCs and the ROS scavenger N-acetylcysteine (NAC). Under SP conditions, HIF-1α(-/-) mESCs failed to increase the expression of endodermal marker genes but rather shifted toward ectoderm. Hypoxia induced only a marginal potentiation of AA-induced endoderm differentiation in HIF-1α(-/-) mESCs. Treatment of mESCs with AA and NAC led to a dose-dependent decrease in Sox17 and Foxa2 expression. In addition, the duration of exposure to hypoxia in the course of a recently reported lung differentiation protocol resulted in differentially enhanced expression of distal lung epithelial cell marker genes aquaporin 5 (Aqp5), surfactant protein C (Sftpc), and secretoglobin 1a1 (Scgb1a1) for alveolar epithelium type I, type II, and club cells, respectively. Our study is the first to show the effects of in vitro hypoxia on efficient formation of DE and lung lineages. We suggest that the extent of hypoxia and careful timing may be important components of in vitro differentiation bioprocesses for the differential generation of distal lung epithelial cells from pluripotent progenitors.
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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.