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Here, we show that MES GSCs exhibit enhanced glycolytic activity and lactate production, driven in part by MES\u2010associated transcriptional regulators that promote LDHA expression. LDHA\u2010derived lactate induces p300\u2010dependent H3K18 lactylation, which enhances USP30 transcription. USP30 subsequently stabilizes the lipid\u2010remodeling enzyme MBOAT2 by limiting its ubiquitination, leading to phosphatidylethanolamine remodeling toward ferroptosis\u2010resistant PE\u2010MUFA species. Disruption of this LDHA\u2013H3K18la\u2013USP30\u2013MBOAT2 axis by LDHA inhibition, impaired H3K18 lactylation, USP30 inhibition, or MBOAT2 depletion increases lipid peroxidation, promotes ferroptosis, and sensitizes MES GSCs to irradiation. Lipid rescue experiments further identify PE\u2010MUFA remodeling as a functional mediator of MBOAT2\u2010dependent ferroptosis resistance. In intracranial xenografts, combined targeting of glycolysis and USP30 enhances radiotherapeutic efficacy without obvious treatment\u2010associated body weight loss under the tested conditions. These findings reveal a metabolic\u2013epigenetic\u2013lipid remodeling circuit that protects MES GSCs from ferroptosis and promotes radioresistance.<\/jats:p>","DOI":"10.1002\/advs.77044","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:52:12Z","timestamp":1786549932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la\/USP30\/MBOAT2 Axis"],"prefix":"10.1002","volume":"13","author":[{"given":"Zong","family":"Miao","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Changhai Hospital Naval Medical University (Second Military Medical University)  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Nanjing 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