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Cortical astrocytic neogenin, a key protein switching HIF1/2ɑ-VEGFa-induced angiogenesis to MEGF10-driven phagocytosis

GSE311122 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2026/01/31 Platform GPL34290
Summary
Astrocytes play key roles in multi-cellular processes in the brain, including maintaining homeostasis of blood vessels (BVs) and clearance of damaged cell debris. The detailed underlying mechanisms remain elusive. Here, we provide evidence that cortical astrocytic neogenin (NEO1) coordinates MEGF10-mediated phagocytosis with HIF1/2ɑ driven VEGFa-induced angiogenesis. Knocking-out (KO) NEO1 in astrocytes increases in HIF1/2ɑ, VEGFa, and immature BVs, but decreases in MEGF10 and MEGF10-regulated phagocytosis, in mouse cortex, but not hippocampus. Further studies suggest that the NEO1-KO impairs prolyl hydroxylase domain protein (PHD) mediated HIF1/2ɑ hydroxylation by inducing iron deficiency, thus increasing HIF1/2ɑ-HIF1b-P300 protein complex driven VEGFa expression at the expense of HIF1β-P300 binding to the MEGF10 promoter; consequently, reducing MEGF10 expression. Thus, these results suggest that cortical astrocytic NEO1 promotes MEGF10 mediated phagocytosis, likely by suppressing HIF1/2ɑ-HIF1β-P300 induced VEGFa.
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Also filed as BioProject PRJNA1368708 and SRA study SRP648312. Searching any of these in the dataset finder brings you back here.

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