Epigenetic encoding, heritability and plasticity of glioma transcriptional cell states.

ABSTRACT: Single-cell RNA sequencing has revealed extensive transcriptional cell state diversity in cancer, often observed independently of genetic heterogeneity, raising the central question of how malignant cell states are encoded epigenetically. To address this, here we performed multiomics single-cell profiling-integrating DNA methylation, transcriptome and genotype within the same cells-of diffuse gliomas, tumors characterized by defined transcriptional cell state diversity. Direct comparison of the epigenetic profiles of distinct cell states revealed key switches for state transitions recapitulating neurodevelopmental trajectories and highlighted dysregulated epigenetic mechanisms underlying gliomagenesis. We further developed a quantitative framework to directly measure cell state heritabilit

SUBMITTER: Chaligne R 

PROVIDER: S-EPMC8675181 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature