{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:45:50Z","timestamp":1792043150892,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100022713","name":"Charlie Teo Foundation","doi-asserted-by":"publisher","award":["PR 10392"],"award-info":[{"award-number":["PR 10392"]}],"id":[{"id":"10.13039\/501100022713","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Adult\u2010type diffuse gliomas are defined by the isocitrate\u2010dehydrogenase (IDH) axis, yet how this biology constrains malignant cell\u2010state repertoires and their immune\u2010modulatory potential remains\u00a0unclear. We profiled 69 tumors using single\u2010cell RNA sequencing (scRNA\u2010seq), single\u2010nucleus RNA sequencing (snRNA\u2010seq), and spatial transcriptomics, and resolved seven recurrent malignant cell states: astrocyte\u2010like progenitor cells (ALPC), hypoxia, cycling G1\/S, cycling G2\/M, oligo\u2010lineage, neuro\u2010oligo\u2010lineage, and neuro\u2010lineage. The\n                    <jats:italic>IDH<\/jats:italic>\n                    axis strongly biased state occupancy and malignant\u2013immune composition, with\n                    <jats:italic>IDH<\/jats:italic>\n                    \u2010mutant tumors dominated by differentiated lineage\u2010like states and reduced immune infiltration, whereas glioblastoma (GBM) showed expansion of ALPC and hypoxia states alongside increased myeloid and lymphoid infiltration. Orthogonal analyses supported that ALPC\u2010associated markers are expressed in situ and in patient\u2010derived stem cell\u2010permissive cultures, consistent with a stem\u2010like, differentiation\u2010competent malignant phenotype. State\u2010resolved pathway analysis identified mitochondrial oxidative phosphorylation programs enriched in GBM ALPC and extracellular matrix remodeling, and chemotaxis\u2010associated programs enriched in GBM hypoxia. Composition\u2010controlled, patient\u2010level interaction modeling identified a greater malignant\u2010myeloid signaling interface in GBM, driven by SPP1\u2013CD44\/integrin signaling and confirmed by differential expression; GBM networks also featured TGFB\u00a0and NECTIN modules, whereas\n                    <jats:italic>IDH<\/jats:italic>\n                    \u2010mutant networks were dominated by APP\/APOE\u2013TREM2\/TYROBP and MIF modules. These data suggest that the IDH axis shapes glioma behavior by constraining malignant state repertoires and biasing the deployment of state\u2010specific metabolic and immunomodulatory programs.\n                  <\/jats:p>","DOI":"10.1002\/mco2.71022","type":"journal-article","created":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:12:12Z","timestamp":1791101532000},"source":"Crossref","is-referenced-by-count":0,"title":["A State\u2010Resolved Single\u2010Cell and Spatial Atlas Reveals\n                    <i>IDH<\/i>\n                    \u2010Associated Differences in Malignant and Immune Architecture in Diffuse Glioma"],"prefix":"10.1002","volume":"7","author":[{"given":"Ashraf","family":"Zaman","sequence":"first","affiliation":[{"name":"Translational Genomics Program, Garvan Institute of Medical Research  Sydney Australia"},{"name":"Faculty of Medicine and Health School of Clinical Medicine University of New South Wales  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Holton","sequence":"additional","affiliation":[{"name":"Translational Genomics Program, Garvan Institute of Medical Research  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhavi","family":"Pandya","sequence":"additional","affiliation":[{"name":"Translational Genomics Program, Garvan Institute of Medical Research  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve","family":"Shillington","sequence":"additional","affiliation":[{"name":"Translational Genomics Program, Garvan Institute of Medical Research  Sydney Australia"},{"name":"Faculty of Medicine and Health, School of Biomedical Sciences, University of New South Wales  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecile","family":"Escher","sequence":"additional","affiliation":[{"name":"Translational Genomics Program, Garvan Institute of Medical Research  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavitha Krishna","family":"Sudhakar","sequence":"additional","affiliation":[{"name":"Translational Genomics Program, Garvan Institute of Medical Research  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agota","family":"Tuzesi","sequence":"additional","affiliation":[{"name":"Translational Genomics Program, Garvan Institute of Medical Research  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Mehta","sequence":"additional","affiliation":[{"name":"Translational Genomics Program, Garvan Institute of Medical Research  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Lam","sequence":"additional","affiliation":[{"name":"Translational Genomics Program, Garvan Institute of Medical Research  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Zekanovic","sequence":"additional","affiliation":[{"name":"Translational Genomics Program, Garvan Institute of Medical Research  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sughrue","sequence":"additional","affiliation":[{"name":"Omniscient Neurotechnology  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Teo","sequence":"additional","affiliation":[{"name":"Cingulum Health Clinic  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacky","family":"Yeung","sequence":"additional","affiliation":[{"name":"Yale School of Medicine  New Haven USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Muskovic","sequence":"additional","affiliation":[{"name":"Translational Genomics Program, Garvan Institute of Medical Research  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Powell","sequence":"additional","affiliation":[{"name":"Translational Genomics Program, Garvan Institute of Medical Research  Sydney Australia"},{"name":"Faculty of Medicine and Health, School of Biomedical Sciences, University of New South Wales  Sydney Australia"},{"name":"UNSW Cellular Genomics Futures Institute University of New South Wales  Sydney 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