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The molecular basis underpinning GSC\u2010GDEC differentiation remain incompletely elucidated. Here, ROR1 is identified as a key regulator of GSC\u2010to\u2010GDEC differentiation under hypoxia. ROR1 expression is elevated in GDECs across patient\u2010derived cells, xenografts, and tumor samples, confirmed by single\u2010cell multiomics, Western blotting, and multiplex staining. Mechanistically, WNT5A, secreted by tumor\u2010associated macrophages (TAMs) under hypoxia, activates ROR1\u2010mediated Wingless\u2010type MMTV integration site family (WNT)\u00a0signaling in GSCs, promoting GDEC formation. Interestingly, hypoxia\u2010induced WTAP not only enhances ROR1 stability through m\n                    <jats:sup>6<\/jats:sup>\n                    A modification in a HuR\u2010dependent manner, but also contributes to WNT5A+TAMs infiltration. Clinically, high ROR1 and WNT5A expression correlates with poor glioblastoma prognosis, and WNT5A may serve as a circulating biomarker. Therapeutically, targeting ROR1 via endothelial\u2010specific Adno\u2010Associated Virus (AAV) knockdown or the antibody\u2010drug conjugate Zilovertamab vedotin (VLS\u2010101) normalizes vasculature, improves temozolomide delivery, and sensitizes tumors in glioblastoma organoids and xenografts. These findings highlight the ROR1\u2013WNT5A axis as a promising target in glioblastomas treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202520661","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T10:43:26Z","timestamp":1768992206000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting WTAP\/ROR1\/WNT5A\u2010Mediated Crosstalk Between Glioma Stem Cells and Macrophages to Normalize Tumor Vasculature and Enhance Chemotherapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaoyong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University  Beijing China"},{"name":"Department of Neurosurgery Neurosurgery Research Institute The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Beijing Neurosurgical Institute Capital Medical University  Beijing 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