Single-cell multi-omics sequencing uncovers region-specific plasticity of glioblastoma for complementary therapeutic targeting.

ABSTRACT: Glioblastoma (GBM) cells are highly heterogeneous and invasive, leading to treatment resistance and relapse. However, the molecular regulation in and distal to tumors remains elusive. Here, we collected paired tissues from the tumor core (TC) and peritumoral brain (PTB) for integrated snRNA-seq and snATAC-seq analyses. Tumor cells infiltrating PTB from TC behave more like oligodendrocyte progenitor cells than astrocytes at the transcriptome level. Dual-omics analyses further suggest that the distal regulatory regions in the tumor genome and specific transcription factors are potential determinants of regional heterogeneity. Notably, while activator protein 1 (AP-1) is active in all GBM states, its activity declines from TC to PTB, with another transcription factor, BACH1, showing the oppos

SUBMITTER: Wang X 

PROVIDER: S-EPMC11584018 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature