Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma.
Claire VinelGabriel RosserLoredana GuglielmiMyrianni ConstantinouNicola PomellaXinyu ZhangJames R BootTania A JonesThomas O MillnerAnaelle A DumasVardhman RakyanJeremy ReesJamie L ThompsonJuho VuononvirtaSuchita NadkarniTedani El AssanNatasha AleyYung-Yao LinPengtao LiuSven NelanderDenise SheerCatherine L R MerryFederica M Marelli-BergSebastian BrandnerSilvia MarinoPublished in: Nature communications (2021)
Epigenetic mechanisms which play an essential role in normal developmental processes, such as self-renewal and fate specification of neural stem cells (NSC) are also responsible for some of the changes in the glioblastoma (GBM) genome. Here we develop a strategy to compare the epigenetic and transcriptional make-up of primary GBM cells (GIC) with patient-matched expanded potential stem cell (EPSC)-derived NSC (iNSC). Using a comparative analysis of the transcriptome of syngeneic GIC/iNSC pairs, we identify a glycosaminoglycan (GAG)-mediated mechanism of recruitment of regulatory T cells (Tregs) in GBM. Integrated analysis of the transcriptome and DNA methylome of GBM cells identifies druggable target genes and patient-specific prediction of drug response in primary GIC cultures, which is validated in 3D and in vivo models. Taken together, we provide a proof of principle that this experimental pipeline has the potential to identify patient-specific disease mechanisms and druggable targets in GBM.
Keyphrases
- induced apoptosis
- neural stem cells
- gene expression
- genome wide
- regulatory t cells
- dna methylation
- cell cycle arrest
- stem cells
- endoplasmic reticulum stress
- signaling pathway
- emergency department
- single cell
- dendritic cells
- rna seq
- immune response
- case report
- cell proliferation
- mesenchymal stem cells
- cell free
- circulating tumor
- bone marrow
- climate change
- data analysis
- genome wide identification