Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response.

ABSTRACT: Glioma intratumoral heterogeneity enables adaptation to challenging microenvironments and contributes to therapeutic resistance. We integrated 914 single-cell DNA methylomes, 55,284 single-cell transcriptomes and bulk multi-omic profiles across 11 adult IDH mutant or IDH wild-type gliomas to delineate sources of intratumoral heterogeneity. We showed that local DNA methylation disorder is associated with cell-cell DNA methylation differences, is elevated in more aggressive tumors, links with transcriptional disruption and is altered during the environmental stress response. Glioma cells under in vitro hypoxic and irradiation stress increased local DNA methylation disorder and shifted cell states. We identified a positive association between genetic and epigenetic instability that was suppor

SUBMITTER: Johnson KC 

PROVIDER: S-EPMC8570135 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature