- Title
- The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location
- Creator
- Liu, Ilon; Jiang, Li; Mire, Hafsa M.; Madlener, Sibylle; Mayr, Lisa; Quezada, Michael A.; Trissal, Maria; Panditharatna, Eshini; Ernst, Kati J.; Vogelzang, Jayne; Gatesman, Taylor A.; Halbert, Matthew E.; Samuelsson, Erik R.; Palova, Hana; Pokorna, P; Sterba, J; Slaby, O; Geyeregger, R; Diaz, A; Findlay, Izac J.; Dun, Matthew D.; Resnick, A; Suvà, ML; Marco Salas, Sergio; Jones, DTW; Agnihotri, S; Svedlund, J; Koschmann, C; Haberler, C; Czech, T; Slavc, I; Cotter, JA; Ligon, KL; Alexandrescu, S; Beck, Alexander; Yung, WKA; Arrillaga-Romany, I; Gojo, J; Monje, M; Nilsson, M; Filbin, MG; Hack, Olivia A.; Jeong, Daeun; Shaw, McKenzie L.; Englinger, Bernhard; LaBelle, Jenna
- Relation
- Nature Genetics Vol. 54, Issue 12, p. 1881-1894
- Publisher Link
- http://dx.doi.org/10.1038/s41588-022-01236-3
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2022
- Description
- Histone 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.
- Subject
- Histone 3 lysine27-to-methionine (H3-K27M); diffuse midline gliomas (DMGs); cancer cells; microenvironment; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1483717
- Identifier
- uon:51182
- Identifier
- ISSN:1061-4036
- Rights
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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