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The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location
I. Liu, L. Jiang, ER. Samuelsson, S. Marco Salas, A. Beck, OA. Hack, D. Jeong, ML. Shaw, B. Englinger, J. LaBelle, HM. Mire, S. Madlener, L. Mayr, MA. Quezada, M. Trissal, E. Panditharatna, KJ. Ernst, J. Vogelzang, TA. Gatesman, ME. Halbert, H....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem, Research Support, N.I.H., Extramural
Grantová podpora
R01 CA219943
NCI NIH HHS - United States
P50 CA165962
NCI NIH HHS - United States
P30 CA014089
NCI NIH HHS - United States
NLK
ProQuest Central
od 2000-01-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 2000-01-01 do Před 1 rokem
Public Health Database (ProQuest)
od 2000-01-01 do Před 1 rokem
- MeSH
- dítě MeSH
- gliom * genetika MeSH
- histony genetika MeSH
- lidé MeSH
- methionin MeSH
- mutace MeSH
- nádorové mikroprostředí genetika MeSH
- Racemethionin MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
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.
Broad Institute of MIT and Harvard Cambridge MA USA
Center for Neuropathology Ludwig Maximilians University Munich Germany
Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic
Department of Neurological Surgery University of California San Francisco San Francisco CA USA
Department of Neurological Surgery University of Pittsburgh School of Medicine Pittsburgh PA USA
Department of Neurosurgery Medical University of Vienna Vienna Austria
Department of Oncologic Pathology Dana Farber Cancer Institute Boston MA USA
Department of Pathology Boston Children's Hospital Boston MA USA
Department of Pathology Brigham and Women's Hospital Boston MA USA
Department of Pathology Center for Cancer Research Massachusetts General Hospital Boston MA USA
Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria
Hopp Children's Cancer Center Heidelberg Heidelberg Germany
Howard Hughes Medical Institute Stanford CA USA
John G Rangos Sr Research Center Children's Hospital of Pittsburgh Pittsburgh PA USA
Citace poskytuje Crossref.org
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- $a The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location / $c I. Liu, L. Jiang, ER. Samuelsson, S. Marco Salas, A. Beck, OA. Hack, D. Jeong, ML. Shaw, B. Englinger, J. LaBelle, HM. Mire, S. Madlener, L. Mayr, MA. Quezada, M. Trissal, E. Panditharatna, KJ. Ernst, J. Vogelzang, TA. Gatesman, ME. Halbert, H. Palova, P. Pokorna, J. Sterba, O. Slaby, R. Geyeregger, A. Diaz, IJ. Findlay, MD. Dun, A. Resnick, ML. Suvà, DTW. Jones, S. Agnihotri, J. Svedlund, C. Koschmann, C. Haberler, T. Czech, I. Slavc, JA. Cotter, KL. Ligon, S. Alexandrescu, WKA. Yung, I. Arrillaga-Romany, J. Gojo, M. Monje, M. Nilsson, MG. Filbin
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