Dataset Information

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-treatment. Blocking P300 histone acetyltransferase activity reverses the epigenetic changes induced by radiation and inhibits the adaptive conversion of GSC into vascular-like cells and tumor growth. Our findings highlight a role for P300 in radiation-induced stress response, suggesting a therapeutic approach to prevent glioma recurrence.

SUBMITTER: Muthukrishnan SD

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

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Muthukrishnan Sree Deepthi SD Kawaguchi Riki R Nair Pooja P Prasad Rachna R Qin Yue Y Johnson Maverick M Wang Qing Q VanderVeer-Harris Nathan N Pham Amy A Alvarado Alvaro G AG Condro Michael C MC Gao Fuying F Gau Raymond R Castro Maria G MG Lowenstein Pedro R PR Deb Arjun A Hinman Jason D JD Pajonk Frank F Burns Terry C TC Goldman Steven A SA Geschwind Daniel H DH Kornblum Harley I HI

Nature communications 20221019 1

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 ...[more]

PMID: 36261421

Similar Datasets

Project description:Purpose: The goal of the study is to determine the phenotypic and functional states of glioma cells induce in response to a standard glioblastoma therapy, ionizing radiation. Methods: We performed single-cell RNA-sequencing on a patient-derived gliomasphere line isolated from a primary glioblastoma tumor. Cells were exposed to a single dose of radiation ( 8 Gy) for 2- and 7-days to elaborate their gene expression profile. Single cell suspensions and cDNA library preparation was done using 10x Genomics Chromium single cell reagent kit v3 according to manufacturer's protocol. cDNA samples were sequenced on 1 lane of NovaSeq 6000 S2 flowcell. Reads were mapped to HumanGRCh38 genome using Cell Ranger v.3.0.2. More than 600 million reads were obtained for each sample. Average number of genes detected was 5875 (SE±357). Confident read mapping rates were 81.2-87.4% with over 86.8% of reads in cells. Seurat package v3.1.1 was used for integrated analysis by Canonical correlation analysis method with 75 dimensions . PCA was used for dimensional reduction, and Cell clustering was performed using shared nearest neighbor method. Each cell cluster was annotated by a combination of the following methods 1) canonical marker expression 2) Gene Set Enrichment Analysis (GSEA) of cluster specific markers determined by Find Markers function in Seurat and 3) Co-expression modules obtained by Louvain community detection clustering method. Trajectory analysis was done with monocle 3 (version 0.2.1.3) by converting Seurat object to monocle. Results: We identified 14 distinct clusters in all samples, and found dynamic alterations in frequency and size of clusters between non-radiated and radiated cells. Louvian community detection and co-expressed gene module analysis revealed that clusters expressing mitotic and DNA repair modules were diminshed, whereas clusters expressing stemness, mesenchymal and vasculogenesis modules increased post-radiation. Conclusion: Radiation therapy induces diverse functional states in glioma cells.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets