Relief of hypoxia by angiogenesis promotes neural stem cell differentiation by targeting glycolysis

Blood vessels are part of the stem cell niche in the developing cerebral cortex, but their in vivo role in controlling the expansion and differentiation of neural stem cells (NSCs) in development has not been studied. Here, we report that relief of hypoxia in the developing cerebral cortex by ingrowth of blood vessels temporo-spatially coincided with NSC differentiation. Selective perturbation of brain angiogenesis in vessel-specific Gpr124 null embryos, which prevented the relief from hypoxia, increased NSC expansion at the expense of differentiation. Conversely, exposure to increased oxygen levels rescued NSC differentiation in Gpr124 null embryos and increased it further in WT embryos, suggesting that niche blood vessels regulate NSC differentiation at least in part by providing oxygen. Consistent herewith, hypoxia-inducible factor (HIF)-1α levels controlled the switch of NSC expansion to differentiation. Finally, we provide evidence that high glycolytic activity of NSCs is required to prevent their precocious differentiation in vivo. Thus, blood vessel function is required for efficient NSC differentiation in the developing cerebral cortex by providing oxygen and possibly regulating NSC metabolism.
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Neuroscience, Vascular Biology & Angiogenesis Articles Source Type: research

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Conditions:   Allogeneic Hematopoietic Stem Cell Transplant Recipient;   Donor;   Malignant Neoplasm Intervention:   Procedure: Biospecimen Collection Sponsors:   City of Hope Medical Center;   National Cancer Institute (NCI) Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Acute Myeloid Leukemia (AML);   Cancer Interventions:   Drug: Venetoclax;   Drug: Azacitidine;   Other: Best Supportive Care (BSC) Sponsor:   AbbVie Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Authors: Ikuno T, Ito S, Inoue T Abstract Mast cells are key players in the inflammatory response with an important role in allergic reactions and are therefore useful for assessing the risk of anaphylaxis. However, they are difficult to isolate due to their low abundance and wide distribution. To overcome this, we generated and characterized mast cell-like cells derived from human induced pluripotent stem (hiPS) cells. These hiPS cell-derived mast cells (hiPS-MCs) were generated using recombinant human bone morphogenetic protein 4 (BMP4), vascular endothelial growth factor 165 (VEGF), stem cell factor (SCF), inter...
Source: Journal of Toxicological Sciences - Category: Toxicology Tags: J Toxicol Sci Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
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Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
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Source: Asian Spine Journal - Category: Orthopaedics Tags: Asian Spine J Source Type: research
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Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
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Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
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Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
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Source: PRWeb: Medical Pharmaceuticals - Category: Pharmaceuticals Source Type: news
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