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Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma

Vinel, Claire (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.
Rosser, Gabriel (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.
Guglielmi, Loredana (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.
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Constantinou, Myrianni (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.
Pomella, Nicola (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.
Zhang, Xinyu (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.
Boot, James R. (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.
Jones, Tania A. (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.
Millner, Thomas O. (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.
Dumas, Anaelle A. (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.
Rakyan, Vardhman (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.
Rees, Jeremy (author)
Univ Coll London Hosp NHS Fdn Trust, Natl Hosp Neurol & Neurosurg, Div Neuropathol, Queen Sq, London, England.
Thompson, Jamie L. (author)
Univ Nottingham, Biodiscovery Inst, Stem Cell Glycobiol Grp, Nottingham, England.
Vuononvirta, Juho (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.
Nadkarni, Suchita (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.
El Assan, Tedani (author)
Univ Coll London Hosp NHS Fdn Trust, Natl Hosp Neurol & Neurosurg, Div Neuropathol, Queen Sq, London, England.
Aley, Natasha (author)
UCL Queen Sq Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London, England.
Lin, Yung-Yao (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.;Queen Mary Univ London, Natl Bowel Res Ctr, Barts & London Sch Med & Dent, Stem Cell Lab, 2 Newark St, London, England.
Liu, Pentao (author)
Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Peoples R China.
Nelander, Sven (author)
Uppsala universitet,Neuroonkologi
Sheer, Denise (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.
Merry, Catherine L. R. (author)
Univ Nottingham, Biodiscovery Inst, Stem Cell Glycobiol Grp, Nottingham, England.
Marelli-Berg, Federica (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.
Brandner, Sebastian (author)
Univ Coll London Hosp NHS Fdn Trust, Natl Hosp Neurol & Neurosurg, Div Neuropathol, Queen Sq, London, England.;UCL Queen Sq Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London, England.
Marino, Silvia (author)
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England.
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Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England Univ Coll London Hosp NHS Fdn Trust, Natl Hosp Neurol & Neurosurg, Div Neuropathol, Queen Sq, London, England. (creator_code:org_t)
2021-10-21
2021
English.
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
Related links:
https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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