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. 2026 Jan 5:e16965.
doi: 10.1002/advs.202516965. Online ahead of print.

Spatially Resolved Multiomics Reveals Metabolic Remodeling and Autophagy Activation in Adamantinomatous Craniopharyngiomas

Dongting Chen  1 , Yahui Gao  2 , Yulin Wang  1 , Ting Lei  3 , Zheng Qu  1 , Yuhan An  1 , Jiaxu Fu  3 , Xin Li  2 , Fangjun Liu  3 , Yan Li  1
Affiliations

Spatially Resolved Multiomics Reveals Metabolic Remodeling and Autophagy Activation in Adamantinomatous Craniopharyngiomas

Dongting Chen et al. Adv Sci (Weinh). .

Abstract

Adamantinomatous craniopharyngioma (ACP), a benign yet highly recurrent and therapy-resistant intracranial tumor, remains a considerable clinical challenge because of its complex pathological structure, infiltrative growth, and limited treatment options. Here, integrated spatially resolved multiomics is employed-including single-cell spatial transcriptomics via CosMx SMI and spatially resolved metabolomics via AFADESI-MSI, accompanied by bulk metabolomics and functional validation-to 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-mediated choline/ethanolamine uptake from cystic fluid and significant upregulation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) synthesis is observed, creating the enhanced "cystic fluid-tumor cell" and "choline/ethanolamine-PC/PE" 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-immunohistochemistry 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-driven treatment of this intractable tumor.

Keywords: adamantinomatous craniopharyngioma; glycerophospholipid metabolism; multiomics; single‐cell spatial transcriptomics; spatially resolved metabolomics.

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