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000182895 0247_ $$2ISSN$$a1546-1718
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000182895 041__ $$aEnglish
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000182895 1001_ $$00000-0002-6186-3630$$aLiu, Ilon$$b0
000182895 245__ $$aThe landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location.
000182895 260__ $$aLondon$$bMacmillan Publishers Limited, part of Springer Nature$$c2022
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000182895 500__ $$a2022 Dec;54(12):1881-1894
000182895 520__ $$aHistone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized in adults. Their potential heterogeneity at different ages and midline locations is vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We show that stem-like oligodendroglial precursor-like cells, present across all clinico-anatomical groups, display varying levels of maturation dependent on location. We reveal a previously underappreciated relationship between mesenchymal cancer cell states and age, linked to age-dependent differences in the immune microenvironment. Further, we resolve the spatial organization of H3-K27M DMG cell populations and identify a mitotic oligodendroglial-lineage niche. Collectively, our study provides a powerful framework for rational modeling and therapeutic interventions.
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000182895 7001_ $$aJiang, Li$$b1
000182895 7001_ $$00000-0002-5622-288X$$aSamuelsson, Erik R$$b2
000182895 7001_ $$aMarco Salas, Sergio$$b3
000182895 7001_ $$aBeck, Alexander$$b4
000182895 7001_ $$aHack, Olivia A$$b5
000182895 7001_ $$aJeong, Daeun$$b6
000182895 7001_ $$aShaw, McKenzie L$$b7
000182895 7001_ $$aEnglinger, Bernhard$$b8
000182895 7001_ $$aLaBelle, Jenna$$b9
000182895 7001_ $$aMire, Hafsa M$$b10
000182895 7001_ $$aMadlener, Sibylle$$b11
000182895 7001_ $$aMayr, Lisa$$b12
000182895 7001_ $$00000-0001-7307-5204$$aQuezada, Michael A$$b13
000182895 7001_ $$aTrissal, Maria$$b14
000182895 7001_ $$aPanditharatna, Eshini$$b15
000182895 7001_ $$0P:(DE-He78)bac03ea8237bbc7b1290321d845ddef7$$aErnst, Kati J$$b16$$udkfz
000182895 7001_ $$aVogelzang, Jayne$$b17
000182895 7001_ $$aGatesman, Taylor A$$b18
000182895 7001_ $$aHalbert, Matthew E$$b19
000182895 7001_ $$aPalova, Hana$$b20
000182895 7001_ $$00000-0003-1037-878X$$aPokorna, Petra$$b21
000182895 7001_ $$aSterba, Jaroslav$$b22
000182895 7001_ $$aSlaby, Ondrej$$b23
000182895 7001_ $$aGeyeregger, Rene$$b24
000182895 7001_ $$00000-0001-9059-9501$$aDiaz, Aaron$$b25
000182895 7001_ $$aFindlay, Izac J$$b26
000182895 7001_ $$aDun, Matthew D$$b27
000182895 7001_ $$aResnick, Adam$$b28
000182895 7001_ $$00000-0001-9898-5351$$aSuvà, Mario L$$b29
000182895 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David T W$$b30$$udkfz
000182895 7001_ $$aAgnihotri, Sameer$$b31
000182895 7001_ $$aSvedlund, Jessica$$b32
000182895 7001_ $$aKoschmann, Carl$$b33
000182895 7001_ $$aHaberler, Christine$$b34
000182895 7001_ $$aCzech, Thomas$$b35
000182895 7001_ $$00000-0002-9419-6790$$aSlavc, Irene$$b36
000182895 7001_ $$00000-0002-1420-3314$$aCotter, Jennifer A$$b37
000182895 7001_ $$00000-0002-7733-600X$$aLigon, Keith L$$b38
000182895 7001_ $$aAlexandrescu, Sanda$$b39
000182895 7001_ $$aYung, W K Alfred$$b40
000182895 7001_ $$aArrillaga-Romany, Isabel$$b41
000182895 7001_ $$aGojo, Johannes$$b42
000182895 7001_ $$00000-0002-3547-237X$$aMonje, Michelle$$b43
000182895 7001_ $$00000-0001-9985-0387$$aNilsson, Mats$$b44
000182895 7001_ $$00000-0002-2613-8126$$aFilbin, Mariella G$$b45
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