Journal Article

DKFZ-2022-02998

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location.

Liu, I. ; Jiang, L. ; Samuelsson, E. R. ; Marco Salas, S. ; Beck, A. ; Hack, O. A. ; Jeong, D. ; Shaw, M. L. ; Englinger, B. ; LaBelle, J. ; Mire, H. M. ; Madlener, S. ; Mayr, L. ; Quezada, M. A. ; Trissal, M. ; Panditharatna, E. ; Ernst, K. J.DKFZ* ; Vogelzang, J. ; Gatesman, T. A. ; Halbert, M. E. ; Palova, H. ; Pokorna, P. ; Sterba, J. ; Slaby, O. ; Geyeregger, R. ; Diaz, A. ; Findlay, I. J. ; Dun, M. D. ; Resnick, A. ; Suvà, M. L. ; Jones, D. T. W.DKFZ* ; Agnihotri, S. ; Svedlund, J. ; Koschmann, C. ; Haberler, C. ; Czech, T. ; Slavc, I. ; Cotter, J. A. ; Ligon, K. L. ; Alexandrescu, S. ; Yung, W. K. A. ; Arrillaga-Romany, I. ; Gojo, J. ; Monje, M. ; Nilsson, M. ; Filbin, M. G.

2022
Macmillan Publishers Limited, part of Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s41588-022-01236-3

Abstract: 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.

Note: 2022 Dec;54(12):1881-1894

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Contributing Institute(s):

1. Pediatric Glioma (B360)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 40 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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