IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-47945-7.html
   My bibliography  Save this article

A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations

Author

Listed:
  • Ingrid M. Saldana-Guerrero

    (The University of Sheffield
    The University of Sheffield
    The University of Sheffield)

  • Luis F. Montano-Gutierrez

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Katy Boswell

    (The University of Sheffield
    The University of Sheffield)

  • Christoph Hafemeister

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Evon Poon

    (The Institute of Cancer Research (ICR) & Royal Marsden NHS Trust)

  • Lisa E. Shaw

    (Medical University of Vienna)

  • Dylan Stavish

    (The University of Sheffield
    The University of Sheffield)

  • Rebecca A. Lea

    (The University of Sheffield
    The University of Sheffield)

  • Sara Wernig-Zorc

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Eva Bozsaky

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Irfete S. Fetahu

    (St. Anna Children’s Cancer Research Institute (CCRI)
    Department of Neurology, Division of Neuropathology and Neurochemistry)

  • Peter Zoescher

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Ulrike Pötschger

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Marie Bernkopf

    (St. Anna Children’s Cancer Research Institute (CCRI)
    Labdia Labordiagnostik GmbH)

  • Andrea Wenninger-Weinzierl

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Caterina Sturtzel

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Celine Souilhol

    (The University of Sheffield
    The University of Sheffield
    Sheffield Hallam University)

  • Sophia Tarelli

    (The University of Sheffield
    The University of Sheffield)

  • Mohamed R. Shoeb

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Polyxeni Bozatzi

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Magdalena Rados

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Maria Guarini

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Michelle C. Buri

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Wolfgang Weninger

    (Medical University of Vienna)

  • Eva M. Putz

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Miller Huang

    (Cancer and Blood Disease Institutes, and The Saban Research Institute
    University of Southern California)

  • Ruth Ladenstein

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Peter W. Andrews

    (The University of Sheffield)

  • Ivana Barbaric

    (The University of Sheffield
    The University of Sheffield)

  • George D. Cresswell

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Helen E. Bryant

    (The University of Sheffield)

  • Martin Distel

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Louis Chesler

    (The Institute of Cancer Research (ICR) & Royal Marsden NHS Trust)

  • Sabine Taschner-Mandl

    (St. Anna Children’s Cancer Research Institute (CCRI))

  • Matthias Farlik

    (Medical University of Vienna)

  • Anestis Tsakiridis

    (The University of Sheffield
    The University of Sheffield)

  • Florian Halbritter

    (St. Anna Children’s Cancer Research Institute (CCRI))

Abstract

Early childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to embryonic tumourigenesis due to a lack of suitable models. Here we employ female human embryonic stem cell (hESC) differentiation and single-cell transcriptome and epigenome analysis to assess the effects of chromosome 17q/1q gains, which are prevalent in the embryonal tumour neuroblastoma (NB). We show that CNAs impair the specification of trunk neural crest (NC) cells and their sympathoadrenal derivatives, the putative cells-of-origin of NB. This effect is exacerbated upon overexpression of MYCN, whose amplification co-occurs with CNAs in NB. Moreover, CNAs potentiate the pro-tumourigenic effects of MYCN and mutant NC cells resemble NB cells in tumours. These changes correlate with a stepwise aberration of developmental transcription factor networks. Together, our results sketch a mechanistic framework for the CNA-driven initiation of embryonal tumours.

Suggested Citation

  • Ingrid M. Saldana-Guerrero & Luis F. Montano-Gutierrez & Katy Boswell & Christoph Hafemeister & Evon Poon & Lisa E. Shaw & Dylan Stavish & Rebecca A. Lea & Sara Wernig-Zorc & Eva Bozsaky & Irfete S. F, 2024. "A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47945-7
    DOI: 10.1038/s41467-024-47945-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-47945-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-47945-7?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. Tim Groningen & Nurdan Akogul & Ellen M. Westerhout & Alvin Chan & Nancy E. Hasselt & Danny A. Zwijnenburg & Marloes Broekmans & Peter Stroeken & Franciska Haneveld & Gerrit K. J. Hooijer & C. Dilara , 2019. "A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    2. Xiaotu Ma & Yu Liu & Yanling Liu & Ludmil B. Alexandrov & Michael N. Edmonson & Charles Gawad & Xin Zhou & Yongjin Li & Michael C. Rusch & John Easton & Robert Huether & Veronica Gonzalez-Pena & Mark , 2018. "Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours," Nature, Nature, vol. 555(7696), pages 371-376, March.
    3. Koen Van den Berge & Hector Roux de Bézieux & Kelly Street & Wouter Saelens & Robrecht Cannoodt & Yvan Saeys & Sandrine Dudoit & Lieven Clement, 2020. "Trajectory-based differential expression analysis for single-cell sequencing data," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    4. Wouter Meuleman & Alexander Muratov & Eric Rynes & Jessica Halow & Kristen Lee & Daniel Bates & Morgan Diegel & Douglas Dunn & Fidencio Neri & Athanasios Teodosiadis & Alex Reynolds & Eric Haugen & Je, 2020. "Index and biological spectrum of human DNase I hypersensitive sites," Nature, Nature, vol. 584(7820), pages 244-251, August.
    5. Jan J. Molenaar & Jan Koster & Danny A. Zwijnenburg & Peter van Sluis & Linda J. Valentijn & Ida van der Ploeg & Mohamed Hamdi & Johan van Nes & Bart A. Westerman & Jennemiek van Arkel & Marli E. Ebus, 2012. "Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes," Nature, Nature, vol. 483(7391), pages 589-593, March.
    6. Irfete S. Fetahu & Wolfgang Esser-Skala & Rohit Dnyansagar & Samuel Sindelar & Fikret Rifatbegovic & Andrea Bileck & Lukas Skos & Eva Bozsaky & Daria Lazic & Lisa Shaw & Marcus Tötzl & Dora Tarlungean, 2023. "Single-cell transcriptomics and epigenomics unravel the role of monocytes in neuroblastoma bone marrow metastasis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Bieke Decaesteker & Amber Louwagie & Siebe Loontiens & Fanny De Vloed & Sarah-Lee Bekaert & Juliette Roels & Suzanne Vanhauwaert & Sara De Brouwer & Ellen Sanders & Alla Berezovskaya & Geertrui Deneck, 2023. "SOX11 regulates SWI/SNF complex components as member of the adrenergic neuroblastoma core regulatory circuitry," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. Cécile Thirant & Agathe Peltier & Simon Durand & Amira Kramdi & Caroline Louis-Brennetot & Cécile Pierre-Eugène & Margot Gautier & Ana Costa & Amandine Grelier & Sakina Zaïdi & Nadège Gruel & Irène Ji, 2023. "Reversible transitions between noradrenergic and mesenchymal tumor identities define cell plasticity in neuroblastoma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    9. Carles A. Boix & Benjamin T. James & Yongjin P. Park & Wouter Meuleman & Manolis Kellis, 2021. "Regulatory genomic circuitry of human disease loci by integrative epigenomics," Nature, Nature, vol. 590(7845), pages 300-307, February.
    10. Myrthala Moreno-Smith & Giorgio Milazzo & Ling Tao & Baharan Fekry & Bokai Zhu & Mahmoud A. Mohammad & Simone Giacomo & Roshan Borkar & Karthik Reddy Kami Reddy & Mario Capasso & Sanjeev A. Vasudevan , 2021. "Restoration of the molecular clock is tumor suppressive in neuroblastoma," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    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. Bieke Decaesteker & Amber Louwagie & Siebe Loontiens & Fanny De Vloed & Sarah-Lee Bekaert & Juliette Roels & Suzanne Vanhauwaert & Sara De Brouwer & Ellen Sanders & Alla Berezovskaya & Geertrui Deneck, 2023. "SOX11 regulates SWI/SNF complex components as member of the adrenergic neuroblastoma core regulatory circuitry," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Milton Pividori & Sumei Lu & Binglan Li & Chun Su & Matthew E. Johnson & Wei-Qi Wei & Qiping Feng & Bahram Namjou & Krzysztof Kiryluk & Iftikhar J. Kullo & Yuan Luo & Blair D. Sullivan & Benjamin F. V, 2023. "Projecting genetic associations through gene expression patterns highlights disease etiology and drug mechanisms," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Stefanie Kirchberger & Mohamed R. Shoeb & Daria Lazic & Andrea Wenninger-Weinzierl & Kristin Fischer & Lisa E. Shaw & Filomena Nogueira & Fikret Rifatbegovic & Eva Bozsaky & Ruth Ladenstein & Bernd Bo, 2024. "Comparative transcriptomics coupled to developmental grading via transgenic zebrafish reporter strains identifies conserved features in neutrophil maturation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Han Wang & Huiying Sun & Bilin Liang & Fang Zhang & Fan Yang & Bowen Cui & Lixia Ding & Xiang Wang & Ronghua Wang & Jiaoyang Cai & Yanjing Tang & Jianan Rao & Wenting Hu & Shuang Zhao & Wenyan Wu & Xi, 2023. "Chromatin accessibility landscape of relapsed pediatric B-lineage acute lymphoblastic leukemia," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Samuel S. Kim & Buu Truong & Karthik Jagadeesh & Kushal K. Dey & Amber Z. Shen & Soumya Raychaudhuri & Manolis Kellis & Alkes L. Price, 2024. "Leveraging single-cell ATAC-seq and RNA-seq to identify disease-critical fetal and adult brain cell types," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    6. Jeff DeMartino & Michael T. Meister & Lindy L. Visser & Mariël Brok & Marian J. A. Groot Koerkamp & Amber K. L. Wezenaar & Laura S. Hiemcke-Jiwa & Terezinha Souza & Johannes H. M. Merks & Anne C. Rios, 2023. "Single-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Denis Houzelstein & Caroline Eozenou & Carlos F. Lagos & Maëva Elzaiat & Joelle Bignon-Topalovic & Inma Gonzalez & Vincent Laville & Laurène Schlick & Somboon Wankanit & Prochi Madon & Jyotsna Kirtane, 2024. "A conserved NR5A1-responsive enhancer regulates SRY in testis-determination," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    8. Chirag Nepal & Jesper B. Andersen, 2023. "Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    9. Erica Butti & Stefano Cattaneo & Marco Bacigaluppi & Marco Cambiaghi & Giulia Maria Scotti & Elena Brambilla & Francesca Ruffini & Giacomo Sferruzza & Maddalena Ripamonti & Fabio Simeoni & Laura Cacci, 2022. "Neural precursor cells tune striatal connectivity through the release of IGFBPL1," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    10. Zhangyuan Pan & Yuelin Yao & Hongwei Yin & Zexi Cai & Ying Wang & Lijing Bai & Colin Kern & Michelle Halstead & Ganrea Chanthavixay & Nares Trakooljul & Klaus Wimmers & Goutam Sahana & Guosheng Su & M, 2021. "Pig genome functional annotation enhances the biological interpretation of complex traits and human disease," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    11. Pingting Ying & Can Chen & Zequn Lu & Shuoni Chen & Ming Zhang & Yimin Cai & Fuwei Zhang & Jinyu Huang & Linyun Fan & Caibo Ning & Yanmin Li & Wenzhuo Wang & Hui Geng & Yizhuo Liu & Wen Tian & Zhiyong, 2023. "Genome-wide enhancer-gene regulatory maps link causal variants to target genes underlying human cancer risk," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    12. David Wang & Mathieu Quesnel-Vallieres & San Jewell & Moein Elzubeir & Kristen Lynch & Andrei Thomas-Tikhonenko & Yoseph Barash, 2023. "A Bayesian model for unsupervised detection of RNA splicing based subtypes in cancers," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    13. Wenpin Hou & Zhicheng Ji & Zeyu Chen & E. John Wherry & Stephanie C. Hicks & Hongkai Ji, 2023. "A statistical framework for differential pseudotime analysis with multiple single-cell RNA-seq samples," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    14. Ulrik Kristoffer Stoltze & Jon Foss-Skiftesvik & Thomas van Overeem Hansen & Simon Rasmussen & Konrad J. Karczewski & Karin A. W. Wadt & Kjeld Schmiegelow, 2024. "The evolutionary impact of childhood cancer on the human gene pool," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    15. Manvendra Singh & Ying Zhao & Vinicius Daguano Gastaldi & Sonja M. Wojcik & Yasmina Curto & Riki Kawaguchi & Ricardo M. Merino & Laura Fernandez Garcia-Agudo & Holger Taschenberger & Nils Brose & Dani, 2023. "Erythropoietin re-wires cognition-associated transcriptional networks," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    16. Hope Mumme & Beena E. Thomas & Swati S. Bhasin & Upaasana Krishnan & Bhakti Dwivedi & Pruthvi Perumalla & Debasree Sarkar & Gulay B. Ulukaya & Himalee S. Sabnis & Sunita I. Park & Deborah DeRyckere & , 2023. "Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    17. Ihab Ansari & Llorenç Solé-Boldo & Meshi Ridnik & Julian Gutekunst & Oliver Gilliam & Maria Korshko & Timur Liwinski & Birgit Jickeli & Noa Weinberg-Corem & Michal Shoshkes-Carmel & Eli Pikarsky & Era, 2023. "TET2 and TET3 loss disrupts small intestine differentiation and homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    18. Kensuke Miyake & Junya Ito & Kazufusa Takahashi & Jun Nakabayashi & Frank Brombacher & Shigeyuki Shichino & Soichiro Yoshikawa & Sachiko Miyake & Hajime Karasuyama, 2024. "Single-cell transcriptomics identifies the differentiation trajectory from inflammatory monocytes to pro-resolving macrophages in a mouse skin allergy model," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    19. Zhuoran Xu & Quan Li & Luigi Marchionni & Kai Wang, 2023. "PhenoSV: interpretable phenotype-aware model for the prioritization of genes affected by structural variants," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    20. Sarah Cappuyns & Gino Philips & Vincent Vandecaveye & Bram Boeckx & Rogier Schepers & Thomas Van Brussel & Ingrid Arijs & Aurelie Mechels & Ayse Bassez & Francesca Lodi & Joris Jaekers & Halit Topal &, 2023. "PD-1- CD45RA+ effector-memory CD8 T cells and CXCL10+ macrophages are associated with response to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    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:15:y:2024:i:1:d:10.1038_s41467-024-47945-7. 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.