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- Title
Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma.
- Authors
Vinel, Claire; Rosser, Gabriel; Guglielmi, Loredana; Constantinou, Myrianni; Pomella, Nicola; Zhang, Xinyu; Boot, James R.; Jones, Tania A.; Millner, Thomas O.; Dumas, Anaelle A.; Rakyan, Vardhman; Rees, Jeremy; Thompson, Jamie L.; Vuononvirta, Juho; Nadkarni, Suchita; El Assan, Tedani; Aley, Natasha; Lin, Yung-Yao; Liu, Pentao; Nelander, Sven
- Abstract
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. The identification of patient-specific disease mechanisms and druggable targets is crucial for precision medicine in glioblastoma. Here, the authors show that comparing patients-matched glioma-initiating cells with neural stem cells enables the discovery of patient-specific mechanisms of disease and the identification of effective drugs
- Subjects
NEURAL stem cells; REGULATORY T cells; GLIOBLASTOMA multiforme; DNA analysis; COMPARATIVE studies; STEM cells; T cells
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-26297-6