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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F22%3A00127554" target="_blank" >RIV/00216224:14110/22:00127554 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/65269705:_____/22:00078128 RIV/00159816:_____/22:00078128

Výsledek na webu

<a href="https://www.nature.com/articles/s41588-022-01236-3" target="_blank" >https://www.nature.com/articles/s41588-022-01236-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41588-022-01236-3" target="_blank" >10.1038/s41588-022-01236-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature Genetics

ISSN

1061-4036

e-ISSN

1546-1718

Svazek periodika

54

Číslo periodika v rámci svazku

December 2022

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

14

Strana od-do

1881-1894

Kód UT WoS článku

000920296200009

EID výsledku v databázi Scopus

2-s2.0-85143286346