P300 promotes tumor recurrence by regulating radiation-induced conversion of glioma stem cells to vascular-like cells.

ABSTRACT: Glioma stem cells (GSC) exhibit plasticity in response to environmental and therapeutic stress leading to tumor recurrence, but the underlying mechanisms remain largely unknown. Here, we employ single-cell and whole transcriptomic analyses to uncover that radiation induces a dynamic shift in functional states of glioma cells allowing for acquisition of vascular endothelial-like and pericyte-like cell phenotypes. These vascular-like cells provide trophic support to promote proliferation of tumor cells, and their selective depletion results in reduced tumor growth post-treatment in vivo. Mechanistically, the acquisition of vascular-like phenotype is driven by increased chromatin accessibility and H3K27 acetylation in specific vascular genes allowing for their increased expression post-treatm

SUBMITTER: Muthukrishnan SD 

PROVIDER: S-EPMC9582000 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature