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Here, integrated spatially resolved multiomics is employed\u2014including single\u2010cell spatial transcriptomics via CosMx SMI and spatially resolved metabolomics via AFADESI\u2010MSI, accompanied by bulk metabolomics and functional validation\u2014to unravel the driving factors of ACP progression and recurrence. Analysis results reveal three interdependent biological hallmarks: first, the spatial segregation and molecular heterogeneity of 10 distinct tumor epithelial cell subpopulations within the ACP, each of which presents unique transcriptional signatures; second, in tumor regions and recurrent tumor epithelium tissues, stronger transporter\u2010mediated choline\/ethanolamine uptake from cystic fluid and significant upregulation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) synthesis is observed, creating the enhanced \u201ccystic fluid\u2013tumor cell\u201d and \u201ccholine\/ethanolamine\u2013PC\/PE\u201d metabolic axis, and demonstrating the spatial metabolic remodeling of ACP; and third, this metabolic axis directly couples to autophagy activation of corresponding regions in ACP tissue, which is validated by multi\u2010immunohistochemistry for Beclin1 and GABARAP. Together, these findings reveal metabolic remodeling and autophagic activation as critical drivers of ACP progression and recurrence and provide an opportunity for precise biomarker\u2010driven treatment of this intractable tumor.<\/jats:p>","DOI":"10.1002\/advs.202516965","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T11:00:56Z","timestamp":1767610856000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spatially Resolved Multiomics Reveals Metabolic Remodeling and Autophagy Activation in Adamantinomatous Craniopharyngiomas"],"prefix":"10.1002","volume":"13","author":[{"given":"Dongting","family":"Chen","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study Department of Pharmacology Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangjun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Sanbo Brain Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6234-3717","authenticated-orcid":false,"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study Department of Pharmacology Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 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