IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-023-44300-0.html
   My bibliography  Save this article

Developmental basis of SHH medulloblastoma heterogeneity

Author

Listed:
  • Maxwell P. Gold

    (Massachusetts Institute of Technology (MIT))

  • Winnie Ong

    (The Hospital for Sick Children
    University of Toronto)

  • Andrew M. Masteller

    (Massachusetts Institute of Technology (MIT))

  • David R. Ghasemi

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)
    Heidelberg University Hospital)

  • Julie Anne Galindo

    (Children’s Hospital Los Angeles (CHLA))

  • Noel R. Park

    (Princeton University
    Princeton University
    Princeton University)

  • Nhan C. Huynh

    (Massachusetts Institute of Technology (MIT))

  • Aneesh Donde

    (Massachusetts Institute of Technology (MIT))

  • Veronika Pister

    (Massachusetts Institute of Technology (MIT))

  • Raul A. Saurez

    (The Hospital for Sick Children)

  • Maria C. Vladoiu

    (The Hospital for Sick Children)

  • Grace H. Hwang

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Tanja Eisemann

    (Sanford Burnham Prebys Medical Discovery Institute)

  • Laura K. Donovan

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Adam D. Walker

    (Children’s Hospital Los Angeles (CHLA))

  • Joseph Benetatos

    (Massachusetts Institute of Technology (MIT))

  • Christelle Dufour

    (Gustave Roussy
    University Paris-Saclay)

  • Livia Garzia

    (McGill University
    McGill University)

  • Rosalind A. Segal

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Robert J. Wechsler-Reya

    (Sanford Burnham Prebys Medical Discovery Institute
    Columbia University Medical Center
    Columbia University Medical Center)

  • Jill P. Mesirov

    (Moores Cancer Center, UC San Diego)

  • Andrey Korshunov

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    German Cancer Research Center (DKFZ)
    German Cancer Consortium (DKTK)
    Heidelberg University Hospital)

  • Kristian W. Pajtler

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)
    Heidelberg University Hospital)

  • Scott L. Pomeroy

    (Boston Children’s Hospital
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Olivier Ayrault

    (PSL Research University
    Université Paris-Saclay, CNRS UMR 3347)

  • Shawn M. Davidson

    (Princeton University
    Rutgers Cancer Institute of New Jersey
    Northwestern University)

  • Jennifer A. Cotter

    (Children’s Hospital Los Angeles (CHLA)
    University of Southern California)

  • Michael D. Taylor

    (The Hospital for Sick Children
    University of Toronto
    The Hospital for Sick Children
    The Hospital for Sick Children)

  • Ernest Fraenkel

    (Massachusetts Institute of Technology (MIT)
    Broad Institute of MIT and Harvard)

Abstract

Many genes that drive normal cellular development also contribute to oncogenesis. Medulloblastoma (MB) tumors likely arise from neuronal progenitors in the cerebellum, and we hypothesized that the heterogeneity observed in MBs with sonic hedgehog (SHH) activation could be due to differences in developmental pathways. To investigate this question, here we perform single-nucleus RNA sequencing on highly differentiated SHH MBs with extensively nodular histology and observed malignant cells resembling each stage of canonical granule neuron development. Through innovative computational approaches, we connect these results to published datasets and find that some established molecular subtypes of SHH MB appear arrested at different developmental stages. Additionally, using multiplexed proteomic imaging and MALDI imaging mass spectrometry, we identify distinct histological and metabolic profiles for highly differentiated tumors. Our approaches are applicable to understanding the interplay between heterogeneity and differentiation in other cancers and can provide important insights for the design of targeted therapies.

Suggested Citation

  • Maxwell P. Gold & Winnie Ong & Andrew M. Masteller & David R. Ghasemi & Julie Anne Galindo & Noel R. Park & Nhan C. Huynh & Aneesh Donde & Veronika Pister & Raul A. Saurez & Maria C. Vladoiu & Grace H, 2024. "Developmental basis of SHH medulloblastoma heterogeneity," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44300-0
    DOI: 10.1038/s41467-023-44300-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44300-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-44300-0?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. Maria C. Vladoiu & Ibrahim El-Hamamy & Laura K. Donovan & Hamza Farooq & Borja L. Holgado & Yogi Sundaravadanam & Vijay Ramaswamy & Liam D. Hendrikse & Sachin Kumar & Stephen C. Mack & John J. Y. Lee , 2019. "Childhood cerebellar tumours mirror conserved fetal transcriptional programs," Nature, Nature, vol. 572(7767), pages 67-73, August.
    2. Volker Hovestadt & Kyle S. Smith & Laure Bihannic & Mariella G. Filbin & McKenzie L. Shaw & Alicia Baumgartner & John C. DeWitt & Andrew Groves & Lisa Mayr & Hannah R. Weisman & Alyssa R. Richman & Ma, 2019. "Resolving medulloblastoma cellular architecture by single-cell genomics," Nature, Nature, vol. 572(7767), pages 74-79, August.
    3. Cedric Ginestet, 2011. "ggplot2: Elegant Graphics for Data Analysis," Journal of the Royal Statistical Society Series A, Royal Statistical Society, vol. 174(1), pages 245-246, January.
    4. Juan Song & Chun Zhong & Michael A. Bonaguidi & Gerald J. Sun & Derek Hsu & Yan Gu & Konstantinos Meletis & Z. Josh Huang & Shaoyu Ge & Grigori Enikolopov & Karl Deisseroth & Bernhard Luscher & Kimber, 2012. "Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision," Nature, Nature, vol. 489(7414), pages 150-154, September.
    5. Patrick Danaher & Pei Wang & Daniela M. Witten, 2014. "The joint graphical lasso for inverse covariance estimation across multiple classes," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 76(2), pages 373-397, March.
    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. 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.
    2. 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.
    3. Meichen Dong & Yiping He & Yuchao Jiang & Fei Zou, 2023. "Joint gene network construction by single‐cell RNA sequencing data," Biometrics, The International Biometric Society, vol. 79(2), pages 915-925, June.
    4. Junliang Yin & Xiaowen Han & Yongxing Zhu & Zhengwu Fang & Derong Gao & Dongfang Ma, 2022. "Transcriptome Profiles of Circular RNAs in Common Wheat during Fusarium Head Blight Disease," Data, MDPI, vol. 7(9), pages 1-8, August.
    5. Kei Hiruma & Seishiro Aoki & Junya Takino & Takeshi Higa & Yuniar Devi Utami & Akito Shiina & Masanori Okamoto & Masami Nakamura & Nanami Kawamura & Yoshihiro Ohmori & Ryohei Sugita & Keitaro Tanoi & , 2023. "A fungal sesquiterpene biosynthesis gene cluster critical for mutualist-pathogen transition in Colletotrichum tofieldiae," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Dong Liu & Changwei Zhao & Yong He & Lei Liu & Ying Guo & Xinsheng Zhang, 2023. "Simultaneous cluster structure learning and estimation of heterogeneous graphs for matrix‐variate fMRI data," Biometrics, The International Biometric Society, vol. 79(3), pages 2246-2259, September.
    7. Mehran Aflakparast & Mathisca de Gunst & Wessel van Wieringen, 2020. "Analysis of Twitter data with the Bayesian fused graphical lasso," PLOS ONE, Public Library of Science, vol. 15(7), pages 1-28, July.
    8. Alessandro Casa & Andrea Cappozzo & Michael Fop, 2022. "Group-Wise Shrinkage Estimation in Penalized Model-Based Clustering," Journal of Classification, Springer;The Classification Society, vol. 39(3), pages 648-674, November.
    9. Wessel N. van Wieringen & Carel F. W. Peeters & Renee X. de Menezes & Mark A. van de Wiel, 2018. "Testing for pathway (in)activation by using Gaussian graphical models," Journal of the Royal Statistical Society Series C, Royal Statistical Society, vol. 67(5), pages 1419-1436, November.
    10. Zaili Luo & Dazhuan Xin & Yunfei Liao & Kalen Berry & Sean Ogurek & Feng Zhang & Liguo Zhang & Chuntao Zhao & Rohit Rao & Xinran Dong & Hao Li & Jianzhong Yu & Yifeng Lin & Guoying Huang & Lingli Xu &, 2023. "Loss of phosphatase CTDNEP1 potentiates aggressive medulloblastoma by triggering MYC amplification and genomic instability," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    11. Gabriela Montejo-Kovacevich & Joana I. Meier & Caroline N. Bacquet & Ian A. Warren & Yingguang Frank Chan & Marek Kucka & Camilo Salazar & Nicol Rueda-M & Stephen H. Montgomery & W. Owen McMillan & Kr, 2022. "Repeated genetic adaptation to altitude in two tropical butterflies," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    12. Byol Kim & Song Liu & Mladen Kolar, 2021. "Two‐sample inference for high‐dimensional Markov networks," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 83(5), pages 939-962, November.
    13. van Wieringen, Wessel N. & Stam, Koen A. & Peeters, Carel F.W. & van de Wiel, Mark A., 2020. "Updating of the Gaussian graphical model through targeted penalized estimation," Journal of Multivariate Analysis, Elsevier, vol. 178(C).
    14. Shanghong Xie & Xiang Li & Peter McColgan & Rachael I. Scahill & Donglin Zeng & Yuanjia Wang, 2020. "Identifying disease‐associated biomarker network features through conditional graphical model," Biometrics, The International Biometric Society, vol. 76(3), pages 995-1006, September.
    15. Sun, Long Long & Hu, Ya Peng & Zhu, Chen Ping, 2023. "Scaling invariance in domestic passenger flight delays in the United States," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 611(C).
    16. Shane Barratt & Stephen Boyd, 2020. "Multi-Period Liability Clearing via Convex Optimal Control," Papers 2005.09066, arXiv.org.
    17. Emma Pierson & the GTEx Consortium & Daphne Koller & Alexis Battle & Sara Mostafavi, 2015. "Sharing and Specificity of Co-expression Networks across 35 Human Tissues," PLOS Computational Biology, Public Library of Science, vol. 11(5), pages 1-19, May.
    18. Joel I. Perez-Perri & Dunja Ferring-Appel & Ina Huppertz & Thomas Schwarzl & Sudeep Sahadevan & Frank Stein & Mandy Rettel & Bruno Galy & Matthias W. Hentze, 2023. "The RNA-binding protein landscapes differ between mammalian organs and cultured cells," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    19. Zongliang Hu & Zhishui Hu & Kai Dong & Tiejun Tong & Yuedong Wang, 2021. "A shrinkage approach to joint estimation of multiple covariance matrices," Metrika: International Journal for Theoretical and Applied Statistics, Springer, vol. 84(3), pages 339-374, April.
    20. Claudia Angelini & Daniela De Canditiis & Anna Plaksienko, 2021. "Jewel : A Novel Method for Joint Estimation of Gaussian Graphical Models," Mathematics, MDPI, vol. 9(17), pages 1-24, August.

    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_s41467-023-44300-0. 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.