ArticleBMC genomics2014
Severe hypoxia exerts parallel and cell-specific regulation of gene expression and alternative splicing in human mesenchymal stem cells.
Article in BMC genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 79 citations in OpenAlex.
- 3D Soft Hydrogels Induce Human Mesenchymal Stem Cells "Deep" Quiescence.Advanced healthcare materials · 2026Article
- Understanding the molecular basis of mesenchymal stem cell stemness: implications for clinical applications.Cell death & disease · 2025Review
- Experience-mediated transcriptional memory correlates with hypoxia resistance in the nervous system of the sea hareAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in Spinal Cord Injury.Molecular neurobiology · 2025Review
- Hypoxic mesenchymal stem cell-derived exosomal circDennd2a regulates granulosa cell glycolysis by interacting with LDHA.Stem cell research & therapy · 2024Article
- The Roles of Exosome-Derived microRNAs in Cardiac Fibrosis.Molecules (Basel, Switzerland) · 2024Review
- Hypoxic-preconditioned mesenchymal stem cell-derived small extracellular vesicles promote the recovery of spinal cord injury by affecting the phenotype of astrocytes through the miR-21/JAK2/STAT3 pathway.CNS neuroscience & therapeutics · 2024Article
- Beyond Traditional Medicine: EVs-Loaded Hydrogels as a Game Changer in Disease Therapeutics.Gels (Basel, Switzerland) · 2024Review
- Mesenchymal Stem Cell-Derived Extracellular Vesicles in Bone-Related Diseases: Intercellular Communication Messengers and Therapeutic Engineering Protagonists.International journal of nanomedicine · 2024Review
- Article
- Engineered mesenchymal stem cell-derived extracellular vesicles: kill tumors and protect organs.Theranostics · 2024Review
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- Breakthrough of extracellular vesicles in pathogenesis, diagnosis and treatment of osteoarthritis.Bioactive materials · 2023Review
- Human Mesenchymal Stem Cell Secretome Driven T Cell Immunomodulation Is IL-10 Dependent.International journal of molecular sciences · 2022Article
- Exosomes secreted by hypoxia-stimulated bone-marrow mesenchymal stem cells promote grafted tendon-bone tunnel healing in rat anterior cruciate ligament reconstruction model.Journal of orthopaedic translation · 2022Article
- Effects of BMSC-Derived EVs on Bone Metabolism.Pharmaceutics · 2022Review
- Characteristics of culture-condition stimulated exosomes or their loaded hydrogels in comparison with other extracellular vesicles or MSC lysates.Frontiers in bioengineering and biotechnology · 2022Review
- Constructing Tissue-Engineered Dressing Membranes with Adipose-Derived Stem Cells and Acellular Dermal Matrix for Diabetic Wound Healing: A Comparative Study of Hypoxia- or Normoxia-Culture Modes.Stem cells international · 2022Article
- The Application of Extracellular Vesicles Mediated miRNAs in Osteoarthritis: Current Knowledge and Perspective.Journal of inflammation research · 2022Review
- Extracellular vesicles derived from mesenchymal stem cells: A platform that can be engineered.Histology and histopathology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe endosteum of the bone marrow provides a specialized hypoxic niche that may serve to preserve the integrity, pluripotency, longevity and stemness of resident mesenchymal stem cells (MSCs). To explore the molecular genetic consequences of such a niche we subjected human (h) MSCs to a pO2 of 4 mmHg and analyzed global gene expression and alternative splicing (AS) by genome-exon microarray and RT-qPCR, and phenotype by western blot and immunostaining.
resultsOut of 446 genes differentially regulated by >2.5-fold, down-regulated genes outnumbered up-regulated genes by 243:203. Exon analyses revealed 60 hypoxia-regulated AS events with splice indices (SI) >1.0 from 53 genes and a correlation between high SI and degree of transcript regulation. Parallel analyses of a publicly available AS study on human umbilical vein endothelial cells (HUVECs) showed that there was a strong cell-specific component with only 11 genes commonly regulated in hMSCs and HUVECs and 17 common differentially spliced genes. Only 3 genes were differentially responsive to hypoxia at the gene (>2.0) and AS levels in both cell types. Functional assignments revealed unique profiles of gene expression with complex regulation of differentiation, extracellular matrix, intermediate filament and metabolic marker genes. Antioxidant genes, striated muscle genes and insulin/IGF-1 signaling intermediates were down-regulated. There was a coordinate induction of 9 out of 12 acidic keratins that along with other epithelial and cell adhesion markers implies a partial mesenchymal to epithelial transition.
conclusionsWe conclude that severe hypoxia confers a quiescent phenotype in hMSCs that is reflected by both the transcriptome profile and gene-specific changes of splicosome actions. The results reveal that severe hypoxia imposes markedly different patterns of gene regulation of MSCs compared with more moderate hypoxia. This is the first study to report hypoxia-regulation of AS in stem/progenitor cells and the first molecular genetic characterization of MSC in a hypoxia-induced quiescent immobile state.
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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.