IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-47280-x.html
   My bibliography  Save this article

Single-cell multiomics reveals the interplay of clonal evolution and cellular plasticity in hepatoblastoma

Author

Listed:
  • Amélie Roehrig

    (INSERM)

  • Theo Z. Hirsch

    (INSERM)

  • Aurore Pire

    (INSERM)

  • Guillaume Morcrette

    (INSERM
    APHP)

  • Barkha Gupta

    (INSERM)

  • Charles Marcaillou

    (IntegraGen SA)

  • Sandrine Imbeaud

    (INSERM)

  • Christophe Chardot

    (Necker Hospital)

  • Emmanuel Gonzales

    (University of Paris-Saclay)

  • Emmanuel Jacquemin

    (University of Paris-Saclay)

  • Masahiro Sekiguchi

    (The University of Tokyo)

  • Junko Takita

    (The University of Tokyo
    Kyoto University)

  • Genta Nagae

    (the University of Tokyo)

  • Eiso Hiyama

    (Hiroshima University Hospital
    Hiroshima University)

  • Florent Guérin

    (Paris-Saclay University)

  • Monique Fabre

    (AP-HP)

  • Isabelle Aerts

    (PSL Research University)

  • Sophie Taque

    (CHU Fontenoy)

  • Véronique Laithier

    (Centre Hospitalier Universitaire Besançon)

  • Sophie Branchereau

    (Paris-Saclay University)

  • Catherine Guettier

    (Paris-Saclay University)

  • Laurence Brugières

    (Department of Children and Adolescents Oncology)

  • Brice Fresneau

    (Department of Children and Adolescents Oncology)

  • Jessica Zucman-Rossi

    (INSERM
    Assistance Publique Hôpitaux de Paris)

  • Eric Letouzé

    (INSERM
    CNRS
    University Hospital Hôtel-Dieu)

Abstract

Hepatoblastomas (HB) display heterogeneous cellular phenotypes that influence the clinical outcome, but the underlying mechanisms are poorly understood. Here, we use a single-cell multiomic strategy to unravel the molecular determinants of this plasticity. We identify a continuum of HB cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activations underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subclone displays its own range of cellular plasticity across differentiation states. The most scLP subclones, overexpressing stem cell and DNA repair genes, proliferate faster after neo-adjuvant chemotherapy. These results highlight how the interplay of clonal evolution and epigenetic plasticity shapes the potential of HB subclones to respond to chemotherapy.

Suggested Citation

  • Amélie Roehrig & Theo Z. Hirsch & Aurore Pire & Guillaume Morcrette & Barkha Gupta & Charles Marcaillou & Sandrine Imbeaud & Christophe Chardot & Emmanuel Gonzales & Emmanuel Jacquemin & Masahiro Seki, 2024. "Single-cell multiomics reveals the interplay of clonal evolution and cellular plasticity in hepatoblastoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47280-x
    DOI: 10.1038/s41467-024-47280-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-47280-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-47280-x?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. Katharina T. Schmid & Barbara Höllbacher & Cristiana Cruceanu & Anika Böttcher & Heiko Lickert & Elisabeth B. Binder & Fabian J. Theis & Matthias Heinig, 2021. "scPower accelerates and optimizes the design of multi-sample single cell transcriptomic studies," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Genta Nagae & Shogo Yamamoto & Masashi Fujita & Takanori Fujita & Aya Nonaka & Takayoshi Umeda & Shiro Fukuda & Kenji Tatsuno & Kazuhiro Maejima & Akimasa Hayashi & Sho Kurihara & Masato Kojima & Tomo, 2021. "Genetic and epigenetic basis of hepatoblastoma diversity," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. Michael Lawrence & Wolfgang Huber & Hervé Pagès & Patrick Aboyoun & Marc Carlson & Robert Gentleman & Martin T Morgan & Vincent J Carey, 2013. "Software for Computing and Annotating Genomic Ranges," PLOS Computational Biology, Public Library of Science, vol. 9(8), pages 1-10, August.
    4. Hanbing Song & Simon Bucher & Katherine Rosenberg & Margaret Tsui & Deviana Burhan & Daniel Hoffman & Soo-Jin Cho & Arun Rangaswami & Marcus Breese & Stanley Leung & María V. Pons Ventura & E. Alejand, 2022. "Single-cell analysis of hepatoblastoma identifies tumor signatures that predict chemotherapy susceptibility using patient-specific tumor spheroids," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Peng V. Wu & Matt Fish & Florette K. Hazard & Chunfang Zhu & Sujay Vennam & Hannah Walton & Dhananjay Wagh & John Coller & Joanna Przybyl & Maurizio Morri & Norma Neff & Robert B. West & Roel Nusse, 2024. "A developmental biliary lineage program cooperates with Wnt activation to promote cell proliferation in hepatoblastoma," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    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. Thomas A. Kluiver & Yuyan Lu & Stephanie A. Schubert & Lianne J. Kraaier & Femke Ringnalda & Philip Lijnzaad & Jeff DeMartino & Wouter L. Megchelenbrink & Vicky Amo-Addae & Selma Eising & Flavia W. Fa, 2024. "Divergent WNT signaling and drug sensitivity profiles within hepatoblastoma tumors and organoids," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Peng V. Wu & Matt Fish & Florette K. Hazard & Chunfang Zhu & Sujay Vennam & Hannah Walton & Dhananjay Wagh & John Coller & Joanna Przybyl & Maurizio Morri & Norma Neff & Robert B. West & Roel Nusse, 2024. "A developmental biliary lineage program cooperates with Wnt activation to promote cell proliferation in hepatoblastoma," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Jie Fang & Shivendra Singh & Changde Cheng & Sivaraman Natarajan & Heather Sheppard & Ahmed Abu-Zaid & Adam D. Durbin & Ha Won Lee & Qiong Wu & Jacob Steele & Jon P. Connelly & Hongjian Jin & Wenan Ch, 2023. "Genome-wide mapping of cancer dependency genes and genetic modifiers of chemotherapy in high-risk hepatoblastoma," Nature Communications, Nature, vol. 14(1), pages 1-27, December.
    4. Poonam Dhillon & Kelly Ann Mulholland & Hailong Hu & Jihwan Park & Xin Sheng & Amin Abedini & Hongbo Liu & Allison Vassalotti & Junnan Wu & Katalin Susztak, 2023. "Increased levels of endogenous retroviruses trigger fibroinflammation and play a role in kidney disease development," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. Andreas Herchenröther & Stefanie Gossen & Tobias Friedrich & Alexander Reim & Nadine Daus & Felix Diegmüller & Jörg Leers & Hakimeh Moghaddas Sani & Sarah Gerstner & Leah Schwarz & Inga Stellmacher & , 2023. "The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    6. Gaylor Boulay & Liliane C. Broye & Rui Dong & Sowmya Iyer & Rajendran Sanalkumar & Yu-Hang Xing & Rémi Buisson & Shruthi Rengarajan & Beverly Naigles & Benoît Duc & Angela Volorio & Mary E. Awad & Raf, 2024. "EWS-WT1 fusion isoforms establish oncogenic programs and therapeutic vulnerabilities in desmoplastic small round cell tumors," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Teresa Maria Rosaria Noviello & Anna Maria Giacomo & Francesca Pia Caruso & Alessia Covre & Roberta Mortarini & Giovanni Scala & Maria Claudia Costa & Sandra Coral & Wolf H. Fridman & Catherine Sautès, 2023. "Guadecitabine plus ipilimumab in unresectable melanoma: five-year follow-up and integrated multi-omic analysis in the phase 1b NIBIT-M4 trial," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Hailyn V. Nielsen & Letitia Yang & James L. Mueller & Alexander J. Ritter & Ryosuke Hiwa & Irina Proekt & Elze Rackaityte & Dominik Aylard & Mansi Gupta & Christopher D. Scharer & Mark S. Anderson & B, 2025. "Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    9. Tiago C. Luis & Nikolaos Barkas & Joana Carrelha & Alice Giustacchini & Stefania Mazzi & Ruggiero Norfo & Bishan Wu & Affaf Aliouat & Jose A. Guerrero & Alba Rodriguez-Meira & Tiphaine Bouriez-Jones &, 2023. "Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. Matthew C. Hill & Bridget Simonson & Carolina Roselli & Ling Xiao & Caroline N. Herndon & Mark Chaffin & Helene Mantineo & Ondine Atwa & Harshit Bhasin & Yasmine Guedira & Kenneth C. Bedi & Kenneth B., 2024. "Large-scale single-nuclei profiling identifies role for ATRNL1 in atrial fibrillation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    11. Michael R. Kelly & Kamila Wisniewska & Matthew J. Regner & Michael W. Lewis & Andrea A. Perreault & Eric S. Davis & Douglas H. Phanstiel & Joel S. Parker & Hector L. Franco, 2022. "A multi-omic dissection of super-enhancer driven oncogenic gene expression programs in ovarian cancer," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    12. Ioanna Tzani & Marina Castro-Rivadeneyra & Paul Kelly & Lisa Strasser & Lin Zhang & Martin Clynes & Barry L. Karger & Niall Barron & Jonathan Bones & Colin Clarke, 2024. "Detection of host cell microprotein impurities in antibody drug products," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    13. Zachary A. Hing & Janek S. Walker & Ethan C. Whipp & Lindsey Brinton & Matthew Cannon & Pu Zhang & Steven Sher & Casey B. Cempre & Fiona Brown & Porsha L. Smith & Claudio Agostinelli & Stefano A. Pile, 2023. "Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter’s transformation," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    14. Brian M. Schilder & Alan E. Murphy & Nathan G. Skene, 2024. "rworkflows: automating reproducible practices for the R community," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    15. F. Nadalin & M. J. Marzi & M. Pirra Piscazzi & P. Fuentes-Bravo & S. Procaccia & M. Climent & P. Bonetti & C. Rubolino & B. Giuliani & I. Papatheodorou & J. C. Marioni & F. Nicassio, 2024. "Multi-omic lineage tracing predicts the transcriptional, epigenetic and genetic determinants of cancer evolution," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    16. Jose V Die & Ransom L Baldwin & Lisa J Rowland & Robert Li & Sunghee Oh & Congjun Li & Erin E Connor & Maria-Jose Ranilla, 2017. "Selection of internal reference genes for normalization of reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis in the rumen epithelium," PLOS ONE, Public Library of Science, vol. 12(2), pages 1-13, February.
    17. Maja Olecka & Alena Bömmel & Lena Best & Madlen Haase & Silke Foerste & Konstantin Riege & Thomas Dost & Stefano Flor & Otto W. Witte & Sören Franzenburg & Marco Groth & Björn Eyss & Christoph Kaleta , 2024. "Nonlinear DNA methylation trajectories in aging male mice," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    18. Eleni Kabrani & Ali Rahjouei & Maria Berruezo-Llacuna & Svenja Ebeling & Tannishtha Saha & Robert Altwasser & Veronica Delgado-Benito & Rushad Pavri & Michela Virgilio, 2025. "RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responses," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    19. Claire Marchal & Nivedita Singh & Zachary Batz & Jayshree Advani & Catherine Jaeger & Ximena Corso-Díaz & Anand Swaroop, 2022. "High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    20. Daniela Klaproth-Andrade & Johannes Hingerl & Yanik Bruns & Nicholas H. Smith & Jakob Träuble & Mathias Wilhelm & Julien Gagneur, 2024. "Deep learning-driven fragment ion series classification enables highly precise and sensitive de novo peptide sequencing," Nature Communications, Nature, vol. 15(1), pages 1-14, 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_s41467-024-47280-x. 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.