{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301613"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"ACSS2 modulates endothelial glycolysis in angiogenesis","description":"Endothelial cells (ECs) sustain high glycolytic flux and display remarkable metabolic plasticity. Although the molecular pathways regulating endothelial glycolysis are well characterized, the metabolic mechanisms underlying hypoxia-induced glycolytic activation during angiogenesis remain poorly understood. Here, we show that acetyl-CoA synthetase 2 (ACSS2) serves as a critical metabolic modulator, coupling acetate utilization with glycolytic flux to control EC function and angiogenesis. The high level of ACSS2-mediated acetate-to-acetyl-CoA conversion in angiogenic front ECs sustains acetyl-CoA levels, which are essential for EC proliferation and retinal vascularization. Conversely, endothelial-specific Acss2 deletion disrupts pathological angiogenesis and normalizes tumor vasculature. Mechanistically, ACSS2 maintains hypoxia-inducible factor 1α transcriptional activity and stabilizes glucose transporter 1, thereby preserving glycolysis. Pyruvate dehydrogenase kinase 4 knockdown rescues metabolic and functional defects in ACSS2-deficient ECs, revealing acetyl-CoA homeostasis as a lynchpin of hypoxic endothelial metabolism. Collectively, our work establishes ACSS2 as a pivotal regulator of vascular development and proposes targeting acetate metabolism as a strategy to modulate pathological angiogenesis.","dates":{"publication":"2026/06/01"},"accession":"GSE301613","cross_references":{"GSM":["GSM9086492","GSM9086496","GSM9086495","GSM9086494","GSM9086493","GSM9086500","GSM9086499","GSM9086498","GSM9086497"],"GPL":["24676"],"GSE":["301613"],"taxon":["Homo sapiens"]}}