IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26297-6.html
   My bibliography  Save this article

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

Author

Listed:
  • Claire Vinel

    (Queen Mary University London)

  • Gabriel Rosser

    (Queen Mary University London)

  • Loredana Guglielmi

    (Queen Mary University London)

  • Myrianni Constantinou

    (Queen Mary University London)

  • Nicola Pomella

    (Queen Mary University London)

  • Xinyu Zhang

    (Queen Mary University London)

  • James R. Boot

    (Queen Mary University London)

  • Tania A. Jones

    (Queen Mary University London)

  • Thomas O. Millner

    (Queen Mary University London)

  • Anaelle A. Dumas

    (Queen Mary University London)

  • Vardhman Rakyan

    (Queen Mary University London)

  • Jeremy Rees

    (University College London Hospitals NHS Foundation Trust)

  • Jamie L. Thompson

    (University of Nottingham)

  • Juho Vuononvirta

    (Queen Mary University London)

  • Suchita Nadkarni

    (Queen Mary University London)

  • Tedani El Assan

    (University College London Hospitals NHS Foundation Trust)

  • Natasha Aley

    (UCL Queen Square Institute of Neurology)

  • Yung-Yao Lin

    (Queen Mary University London
    Queen Mary University of London)

  • Pentao Liu

    (The University of Hong Kong)

  • Sven Nelander

    (Uppsala University)

  • Denise Sheer

    (Queen Mary University London)

  • Catherine L. R. Merry

    (University of Nottingham)

  • Federica Marelli-Berg

    (Queen Mary University London)

  • Sebastian Brandner

    (University College London Hospitals NHS Foundation Trust
    UCL Queen Square Institute of Neurology)

  • Silvia Marino

    (Queen Mary University London)

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.

Suggested Citation

  • Claire Vinel & Gabriel Rosser & Loredana Guglielmi & Myrianni Constantinou & Nicola Pomella & Xinyu Zhang & James R. Boot & Tania A. Jones & Thomas O. Millner & Anaelle A. Dumas & Vardhman Rakyan & Je, 2021. "Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26297-6
    DOI: 10.1038/s41467-021-26297-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26297-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-26297-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Ryan Lister & Mattia Pelizzola & Yasuyuki S. Kida & R. David Hawkins & Joseph R. Nery & Gary Hon & Jessica Antosiewicz-Bourget & Ronan O’Malley & Rosa Castanon & Sarit Klugman & Michael Downes & Ruth , 2011. "Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells," Nature, Nature, vol. 471(7336), pages 68-73, March.
    2. Charles P. Couturier & Shamini Ayyadhury & Phuong U. Le & Javad Nadaf & Jean Monlong & Gabriele Riva & Redouane Allache & Salma Baig & Xiaohua Yan & Mathieu Bourgey & Changseok Lee & Yu Chang David Wa, 2020. "Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
    3. Joo Ho Lee & Jeong Eun Lee & Jee Ye Kahng & Se Hoon Kim & Jun Sung Park & Seon Jin Yoon & Ji-Yong Um & Woo Kyeong Kim & June-Koo Lee & Junseong Park & Eui Hyun Kim & Ji-Hyun Lee & Joon-Hyuk Lee & Won-, 2018. "Human glioblastoma arises from subventricular zone cells with low-level driver mutations," Nature, Nature, vol. 560(7717), pages 243-247, August.
    4. Igor Kogut & Sandra M. McCarthy & Maryna Pavlova & David P. Astling & Xiaomi Chen & Ana Jakimenko & Kenneth L. Jones & Andrew Getahun & John C. Cambier & Anna M. G. Pasmooij & Marcel F. Jonkman & Denn, 2018. "High-efficiency RNA-based reprogramming of human primary fibroblasts," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    5. David Capper & David T. W. Jones & Martin Sill & Volker Hovestadt & Daniel Schrimpf & Dominik Sturm & Christian Koelsche & Felix Sahm & Lukas Chavez & David E. Reuss & Annekathrin Kratz & Annika K. We, 2018. "DNA methylation-based classification of central nervous system tumours," Nature, Nature, vol. 555(7697), pages 469-474, March.
    6. Jere Weltner & Diego Balboa & Shintaro Katayama & Maxim Bespalov & Kaarel Krjutškov & Eeva-Mari Jouhilahti & Ras Trokovic & Juha Kere & Timo Otonkoski, 2018. "Human pluripotent reprogramming with CRISPR activators," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    7. Jian Yang & David J. Ryan & Wei Wang & Jason Cheuk-Ho Tsang & Guocheng Lan & Hideki Masaki & Xuefei Gao & Liliana Antunes & Yong Yu & Zhexin Zhu & Juexuan Wang & Aleksandra A. Kolodziejczyk & Lia S. C, 2017. "Establishment of mouse expanded potential stem cells," Nature, Nature, vol. 550(7676), pages 393-397, October.
    8. Sheila K. Singh & Cynthia Hawkins & Ian D. Clarke & Jeremy A. Squire & Jane Bayani & Takuichiro Hide & R. Mark Henkelman & Michael D. Cusimano & Peter B. Dirks, 2004. "Identification of human brain tumour initiating cells," Nature, Nature, vol. 432(7015), pages 396-401, November.
    9. Xiaoyang Lan & David J. Jörg & Florence M. G. Cavalli & Laura M. Richards & Long V. Nguyen & Robert J. Vanner & Paul Guilhamon & Lilian Lee & Michelle M. Kushida & Davide Pellacani & Nicole I. Park & , 2017. "Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy," Nature, Nature, vol. 549(7671), pages 227-232, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Akram A. Hamed & Daniel J. Kunz & Ibrahim El-Hamamy & Quang M. Trinh & Omar D. Subedar & Laura M. Richards & Warren Foltz & Garrett Bullivant & Matthaeus Ware & Maria C. Vladoiu & Jiao Zhang & Antony , 2022. "A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Norman L. Lehman & Nathalie Spassky & Müge Sak & Amy Webb & Cory T. Zumbar & Aisulu Usubalieva & Khaled J. Alkhateeb & Joseph P. McElroy & Kirsteen H. Maclean & Paolo Fadda & Tom Liu & Vineela Gangala, 2022. "Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Francesco Antonica & Lucia Santomaso & Davide Pernici & Linda Petrucci & Giuseppe Aiello & Alessandro Cutarelli & Luciano Conti & Alessandro Romanel & Evelina Miele & Toma Tebaldi & Luca Tiberi, 2022. "A slow-cycling/quiescent cells subpopulation is involved in glioma invasiveness," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Cristiana Spinelli & Lata Adnani & Brian Meehan & Laura Montermini & Sidong Huang & Minjun Kim & Tamiko Nishimura & Sidney E. Croul & Ichiro Nakano & Yasser Riazalhosseini & Janusz Rak, 2024. "Mesenchymal glioma stem cells trigger vasectasia—distinct neovascularization process stimulated by extracellular vesicles carrying EGFR," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Maria Pouyiourou & Bianca N. Kraft & Timothy Wohlfromm & Michael Stahl & Boris Kubuschok & Harald Löffler & Ulrich T. Hacker & Gerdt Hübner & Lena Weiss & Michael Bitzer & Thomas Ernst & Philipp Schüt, 2023. "Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    6. Xi Lu & Naga Prathyusha Maturi & Malin Jarvius & Irem Yildirim & Yonglong Dang & Linxuan Zhao & Yuan Xie & E-Jean Tan & Pengwei Xing & Rolf Larsson & Mårten Fryknäs & Lene Uhrbom & Xingqi Chen, 2022. "Cell-lineage controlled epigenetic regulation in glioblastoma stem cells determines functionally distinct subgroups and predicts patient survival," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Anyou Wang & Ying Du & Qianchuan He & Chunxiao Zhou, 2013. "A Quantitative System for Discriminating Induced Pluripotent Stem Cells, Embryonic Stem Cells and Somatic Cells," PLOS ONE, Public Library of Science, vol. 8(2), pages 1-10, February.
    8. Paweł Wańkowicz & Przemysław Nowacki & Bogusław Machaliński & Dorota Rogińska, 2019. "Biomarkers of Cancer Stem Cells in Glioblastoma Multiforme and Histological Picture of Cancer," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 23(3), pages 17365-17368, December.
    9. Ravinder K. Bahia & Xiaoguang Hao & Rozina Hassam & Orsolya Cseh & Danielle A. Bozek & H. Artee Luchman & Samuel Weiss, 2023. "Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    10. Lakhal-Chaieb Lajmi & Greenwood Celia M.T. & Ouhourane Mohamed & Zhao Kaiqiong & Abdous Belkacem & Oualkacha Karim, 2017. "A smoothed EM-algorithm for DNA methylation profiles from sequencing-based methods in cell lines or for a single cell type," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 16(5-6), pages 333-347, December.
    11. Josefine Radke & Elisa Schumann & Julia Onken & Randi Koll & Güliz Acker & Bohdan Bodnar & Carolin Senger & Sascha Tierling & Markus Möbs & Peter Vajkoczy & Anna Vidal & Sandra Högler & Petra Kodajova, 2022. "Decoding molecular programs in melanoma brain metastases," Nature Communications, Nature, vol. 13(1), pages 1-24, December.
    12. David R. Ghasemi & Konstantin Okonechnikov & Anne Rademacher & Stephan Tirier & Kendra K. Maass & Hanna Schumacher & Piyush Joshi & Maxwell P. Gold & Julia Sundheimer & Britta Statz & Ahmet S. Rifaiog, 2024. "Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    13. Konstantin Okonechnikov & Aylin Camgöz & Owen Chapman & Sameena Wani & Donglim Esther Park & Jens-Martin Hübner & Abhijit Chakraborty & Meghana Pagadala & Rosalind Bump & Sahaana Chandran & Katerina K, 2023. "3D genome mapping identifies subgroup-specific chromosome conformations and tumor-dependency genes in ependymoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    14. Grayson A. Herrgott & James M. Snyder & Ruicong She & Tathiane M. Malta & Thais S. Sabedot & Ian Y. Lee & Jacob Pawloski & Guilherme G. Podolsky-Gondim & Karam P. Asmaro & Jiaqi Zhang & Cara E. Cannel, 2023. "Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    15. Shicai Chen & Xinming Song & Zhihui Chen & Xinxin Li & Mingzhe Li & Haiying Liu & Jianchang Li, 2013. "CD133 Expression and the Prognosis of Colorectal Cancer: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(2), pages 1-9, February.
    16. Tayma Handal & Sarah Juster & Manar Abu Diab & Shira Yanovsky-Dagan & Fouad Zahdeh & Uria Aviel & Roni Sarel-Gallily & Shir Michael & Ester Bnaya & Shulamit Sebban & Yosef Buganim & Yotam Drier & Vinc, 2024. "Differentiation shifts from a reversible to an irreversible heterochromatin state at the DM1 locus," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    17. Jie Yang & Qianghu Wang & Ze-Yan Zhang & Lihong Long & Ravesanker Ezhilarasan & Jerome M. Karp & Aristotelis Tsirigos & Matija Snuderl & Benedikt Wiestler & Wolfgang Wick & Yinsen Miao & Jason T. Huse, 2022. "DNA methylation-based epigenetic signatures predict somatic genomic alterations in gliomas," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    18. Anne Senabouth & Maciej Daniszewski & Grace E. Lidgerwood & Helena H. Liang & Damián Hernández & Mehdi Mirzaei & Stacey N. Keenan & Ran Zhang & Xikun Han & Drew Neavin & Louise Rooney & Maria Isabel G, 2022. "Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    19. Sun Shuying & Yu Xiaoqing, 2016. "HMM-Fisher: identifying differential methylation using a hidden Markov model and Fisher’s exact test," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 15(1), pages 55-67, March.
    20. Yu Xiaoqing & Sun Shuying, 2016. "HMM-DM: identifying differentially methylated regions using a hidden Markov model," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 15(1), pages 69-81, March.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26297-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.