ArticleMolecular neurobiology2023
Hypoxia Induces Early Neurogenesis in Human Fetal Neural Stem Cells by Activating the WNT Pathway.
Article in Molecular neurobiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 10 citations in OpenAlex.
- Broca's area, responsible for speech production, is regulated by lung function.Neural regeneration research · 2026Article
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- Nrf2 overexpression reprograms neural stem cell fate: promoting neuronal differentiation and functional recovery post-ischemic stroke via suppression of the ROS/NF-κB axis.Journal of translational medicine · 2026Article
- Modeling cerebral developmentbioRxiv : the preprint server for biology · 2025Article
- Hyperoxia shows duration-dependent effects on the lengths of cell cycle phases in fetal cortical neural stem cells.Frontiers in cell and developmental biology · 2025Article
- Using Human Fetal Neural Stem Cells to Elucidate the Role of the JAK-STAT Cell Signaling Pathway in Oligodendrocyte Differentiation In Vitro.Molecular neurobiology · 2024Article
- Reprogramming Glioblastoma Cells into Non-Cancerous Neuronal Cells as a Novel Anti-Cancer Strategy.Cells · 2024Article
- The Brain at High Altitude: From Molecular Signaling to Cognitive Performance.International journal of molecular sciences · 2023Review
- Review
- Acute Prenatal Hypoxia in Rats Affects Physiology and Brain Metabolism in the Offspring, Dependent on Sex and Gestational Age.International journal of molecular sciences · 2022Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Fetal neural stem cells (FNSCs) present in the human fetal brain differentiate into cells of neuronal and glial lineages. The developing fetus is exposed to lower oxygen concentrations than adults, and this physiological hypoxia may influence the growth and differentiation of the FNSCs. This study aimed to evaluate the effect of hypoxia on the differentiation potential of human FNSCs isolated from the subventricular zone of aborted fetal brains (n = 5). FNSCs were isolated, expanded, and characterized by Nestin and Sox2 expression using immunocytochemistry and flow cytometry, respectively. These FNSCs were exposed to 20% oxygen (normoxia) and 0.2% oxygen (hypoxia) concentrations for 48 h, and hypoxia exposure (n = 5) was validated. Whole transcriptome analyses (Genespring GX13) of FNSCs exposed to hypoxia (Agilent 4 × 44 K human array slides) highlighted that genes associated with neurogenesis were enriched upon exposure to hypoxia. The pathway analysis of these enriched genes (using Metacore) showed the involvement of the WNT signaling pathway. Microarray analyses were validated using neuronal and glial lineage commitment markers, namely, NEUROG1, NEUROG2, ASCL1, DCX, GFAP, OLIG2, and NKX2.2, using qPCR (n = 9). DCX, ASCL1, NGN1, and GFAP protein expression was analyzed by Western blotting (n = 3). This demonstrated upregulation of the neuronal commitment markers upon hypoxia exposure, while no change was observed in astrocytic and oligodendrocyte lineage commitment markers. Increased expression of downstream targets of the WNT signaling pathway, TCF4 and ID2, by qPCR (n = 9) and increased protein expression of CTNNB1 (β-catenin) and ID2 by Western blot (n = 3) indicated its involvement in mediating neuronal differentiation upon exposure to hypoxia.
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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.