Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma
Autor: | James R. Boot, Denise Sheer, Vardhman K. Rakyan, Catherine L.R. Merry, Claire Vinel, Sebastian Brandner, Sven Nelander, Yung-Yao Lin, Suchita Nadkarni, Tedani El Assan, Juho Vuononvirta, Thomas O Millner, Federica M. Marelli-Berg, Myrianni Constantinou, Loredana Guglielmi, Jamie L. Thompson, Xinyu Zhang, Gabriel Rosser, Tania A. Jones, Pentao Liu, Nicola Pomella, Anaelle A. Dumas, Jeremy Rees, Natasha Aley, Silvia Marino |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Epigenomics
Transcription Genetic Cell- och molekylärbiologi Science Druggability General Physics and Astronomy Biology General Biochemistry Genetics and Molecular Biology Article Epigenesis Genetic Transcriptome Mice Neural Stem Cells Animals Humans Epigenetics Gene Multidisciplinary Mechanism (biology) Brain Neoplasms Reprogramming Cell Differentiation General Chemistry DNA Methylation Neural stem cell nervous system diseases CNS cancer DNA methylation Cancer research Neoplastic Stem Cells Stem cell Glioblastoma Cell and Molecular Biology |
Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-20 (2021) Nature Communications |
ISSN: | 2041-1723 |
Popis: | 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 |
Databáze: | OpenAIRE |
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