The landscape of tumor cell states and spatial organization in
H3-K27M mutant diffuse midline glioma across age and location

J 2022

The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location

LIU, I., L. JIANG, E. R. SAMUELSSON, S. MARCO SALAS, A. BECK et. al.

Basic information

Original name

The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location

Authors

LIU, I. (guarantor), L. JIANG, E. R. SAMUELSSON, S. MARCO SALAS, A. BECK, O. A. HACK, D. JEONG, M. L. SHAW, B. ENGLINGER, J. LABELLE, H. M. MIRE, S. MADLENER, L. MAYR, M. A. QUEZADA, M. TRISSAL, E. PANDITHARATNA, K. J. ERNST, J. VOGELZANG, T. A. GATESMAN, M. E. HALBERT, Hana PÁLOVÁ (203 Czech Republic, belonging to the institution), Petra POKORNÁ (203 Czech Republic, belonging to the institution), Jaroslav ŠTĚRBA (203 Czech Republic, belonging to the institution), Ondřej SLABÝ (203 Czech Republic, belonging to the institution), R. GEYEREGGER, A. DIAZ, I. J. FINDLAY, M. D. DUN, A. RESNICK, M. L SUVÀ., D. T. W. JONES, S. AGNIHOTRI, J. SVEDLUND, C. KOSCHMANN, C. HABERLER, T. CZECH, I. SLAVC, J. A. COTTER, K. L. LIGON, S. ALEXANDRESCU, W. K. A. YUNG, I. ARRILLAGA-ROMANY, J. GOJO, M. MONJE, M. NILSSON and M. G. FILBIN

Edition

Nature Genetics, BERLIN, NATURE PORTFOLIO, 2022, 1061-4036

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 30.800

RIV identification code

RIV/00216224:14110/22:00127554

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1038/s41588-022-01236-3

UT WoS

000920296200009

Keywords in English

Ageing; Cancer microenvironment; CNS cancer; Transcriptomics

Abstract

V originále

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.

Links

LX22NPO5102, research and development project

Name: Národní ústav pro výzkum rakoviny (Acronym: NÚVR)

Investor: Ministry of Education, Youth and Sports of the CR, National institute for cancer research, 5.1 EXCELES

MUNI/A/1427/2021, interní kód MU

Name: Personalizovaná léčba v dětské onkologii: na cestě k „liquid dynamic medicine“ a „N-of-1 clinical trials“

Investor: Masaryk University

NU20-03-00240, research and development project

Name: Celoexomové sekvenování, sekvenování genomu s nízkým pokrytím a transkriptomu pro účely precizní onkologie u dětských pacientů s vysoce rizikovými a relabovanými solidními nádory

Investor: Ministry of Health of the CR, Whole exome, low-coverage genome and transcriptome sequencing as tools for precision oncology in paediatric patients with high-risk and relapsed solid tumors, Subprogram 1 - standard

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Citovat

LIU, I., L. JIANG, E. R. SAMUELSSON, S. MARCO SALAS, A. BECK, O. A. HACK, D. JEONG, M. L. SHAW, B. ENGLINGER, J. LABELLE, H. M. MIRE, S. MADLENER, L. MAYR, M. A. QUEZADA, M. TRISSAL, E. PANDITHARATNA, K. J. ERNST, J. VOGELZANG, T. A. GATESMAN, M. E. HALBERT, Hana PÁLOVÁ, Petra POKORNÁ, Jaroslav ŠTĚRBA, Ondřej SLABÝ, R. GEYEREGGER, A. DIAZ, I. J. FINDLAY, M. D. DUN, A. RESNICK, M. L SUVÀ., D. T. W. JONES, S. AGNIHOTRI, J. SVEDLUND, C. KOSCHMANN, C. HABERLER, T. CZECH, I. SLAVC, J. A. COTTER, K. L. LIGON, S. ALEXANDRESCU, W. K. A. YUNG, I. ARRILLAGA-ROMANY, J. GOJO, M. MONJE, M. NILSSON and M. G. FILBIN. The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location. Nature Genetics. BERLIN: NATURE PORTFOLIO, 2022, vol. 54, December 2022, p. 1881-1894. ISSN 1061-4036. Available from: https://dx.doi.org/10.1038/s41588-022-01236-3.

@article{2241228,
   author = {Liu, I. and Jiang, L. and Samuelsson, E. R. and Marco Salas, S. and Beck, A. and Hack, O. A. and Jeong, D. and Shaw, M. L. and Englinger, B. and LaBelle, J. and Mire, H. M. and Madlener, S. and Mayr, L. and Quezada, M. A. and Trissal, M. and Panditharatna, E. and Ernst, K. J. and Vogelzang, J. and Gatesman, T. A. and Halbert, M. E. and Pálová, Hana and Pokorná, Petra and Štěrba, Jaroslav and Slabý, Ondřej and Geyeregger, R. and Diaz, A. and Findlay, I. J. and Dun, M. D. and Resnick, A. and Suvà., M. L and Jones, D. T. W. and Agnihotri, S. and Svedlund, J. and Koschmann, C. and Haberler, C. and Czech, T. and Slavc, I. and Cotter, J. A. and Ligon, K. L. and Alexandrescu, S. and Yung, W. K. A. and ArrillagaandRomany, I. and Gojo, J. and Monje, M. and Nilsson, M. and Filbin, M. G.},
   article_location = {BERLIN},
   article_number = {December 2022},
   doi = {http://dx.doi.org/10.1038/s41588-022-01236-3},
   keywords = {Ageing; Cancer microenvironment; CNS cancer; Transcriptomics},
   language = {eng},
   issn = {1061-4036},
   journal = {Nature Genetics},
   title = {The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location},
   url = {https://www.nature.com/articles/s41588-022-01236-3},
   volume = {54},
   year = {2022}
}

TY  - JOUR
ID  - 2241228
AU  - 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. - Vogelzang, J. - Gatesman, T. A. - Halbert, M. E. - Pálová, Hana - Pokorná, Petra - Štěrba, Jaroslav - Slabý, Ondřej - Geyeregger, R. - Diaz, A. - Findlay, I. J. - Dun, M. D. - Resnick, A. - Suvà., M. L - Jones, D. T. W. - 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.
PY  - 2022
TI  - The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location
JF  - Nature Genetics
VL  - 54
IS  - December 2022
SP  - 1881-1894
EP  - 1881-1894
PB  - NATURE PORTFOLIO
SN  - 10614036
KW  - Ageing
KW  - Cancer microenvironment
KW  - CNS cancer
KW  - Transcriptomics
UR  - https://www.nature.com/articles/s41588-022-01236-3
N2  - 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.
ER  -

LIU, I., L. JIANG, E. R. SAMUELSSON, S. MARCO SALAS, A. BECK, O. A. HACK, D. JEONG, M. L. SHAW, B. ENGLINGER, J. LABELLE, H. M. MIRE, S. MADLENER, L. MAYR, M. A. QUEZADA, M. TRISSAL, E. PANDITHARATNA, K. J. ERNST, J. VOGELZANG, T. A. GATESMAN, M. E. HALBERT, Hana PÁLOVÁ, Petra POKORNÁ, Jaroslav ŠTĚRBA, Ondřej SLABÝ, R. GEYEREGGER, A. DIAZ, I. J. FINDLAY, M. D. DUN, A. RESNICK, M. L SUVÀ., D. T. W. JONES, S. AGNIHOTRI, J. SVEDLUND, C. KOSCHMANN, C. HABERLER, T. CZECH, I. SLAVC, J. A. COTTER, K. L. LIGON, S. ALEXANDRESCU, W. K. A. YUNG, I. ARRILLAGA-ROMANY, J. GOJO, M. MONJE, M. NILSSON and M. G. FILBIN. The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location. \textit{Nature Genetics}. BERLIN: NATURE PORTFOLIO, 2022, vol.~54, December 2022, p.~1881-1894. ISSN~1061-4036. Available from: https://dx.doi.org/10.1038/s41588-022-01236-3.

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