Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 10 2021
21 10 2021
Historique:
received:
02
03
2021
accepted:
23
09
2021
entrez:
22
10
2021
pubmed:
23
10
2021
medline:
15
12
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34675201
doi: 10.1038/s41467-021-26297-6
pii: 10.1038/s41467-021-26297-6
pmc: PMC8531305
doi:
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6130Subventions
Organisme : Cancer Research UK
ID : C23985/A29199
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/14/2/30616
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/16/18/31973
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/15/2/32064
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0901084
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/11/64/28945
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/20/8/34995
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0701165
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/09/002/26425
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/14/84/31136
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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