TY  - JOUR
AU  - Liu, Ilon
AU  - Jiang, Li
AU  - Samuelsson, Erik R
AU  - Marco Salas, Sergio
AU  - Beck, Alexander
AU  - Hack, Olivia A
AU  - Jeong, Daeun
AU  - Shaw, McKenzie L
AU  - Englinger, Bernhard
AU  - LaBelle, Jenna
AU  - Mire, Hafsa M
AU  - Madlener, Sibylle
AU  - Mayr, Lisa
AU  - Quezada, Michael A
AU  - Trissal, Maria
AU  - Panditharatna, Eshini
AU  - Ernst, Kati J
AU  - Vogelzang, Jayne
AU  - Gatesman, Taylor A
AU  - Halbert, Matthew E
AU  - Palova, Hana
AU  - Pokorna, Petra
AU  - Sterba, Jaroslav
AU  - Slaby, Ondrej
AU  - Geyeregger, Rene
AU  - Diaz, Aaron
AU  - Findlay, Izac J
AU  - Dun, Matthew D
AU  - Resnick, Adam
AU  - Suvà, Mario L
AU  - Jones, David T W
AU  - Agnihotri, Sameer
AU  - Svedlund, Jessica
AU  - Koschmann, Carl
AU  - Haberler, Christine
AU  - Czech, Thomas
AU  - Slavc, Irene
AU  - Cotter, Jennifer A
AU  - Ligon, Keith L
AU  - Alexandrescu, Sanda
AU  - Yung, W K Alfred
AU  - Arrillaga-Romany, Isabel
AU  - Gojo, Johannes
AU  - Monje, Michelle
AU  - Nilsson, Mats
AU  - Filbin, Mariella G
TI  - The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location.
JO  - Nature genetics
VL  - 54
IS  - 12
SN  - 1061-4036
CY  - London
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - DKFZ-2022-02998
SP  - 1881-1894
PY  - 2022
N1  - 2022 Dec;54(12):1881-1894
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:36471067
DO  - DOI:10.1038/s41588-022-01236-3
UR  - https://inrepo02.dkfz.de/record/182895
ER  -