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Single cell derived mRNA signals across human kidney tumors

Author

Listed:
  • Matthew D. Young

    (Wellcome Genome Campus, Hinxton)

  • Thomas J. Mitchell

    (Wellcome Genome Campus, Hinxton
    Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Lars Custers

    (Princess Máxima Center for Pediatric Oncology
    Oncode Institute)

  • Thanasis Margaritis

    (Princess Máxima Center for Pediatric Oncology)

  • Francisco Morales-Rodriguez

    (Princess Máxima Center for Pediatric Oncology
    Oncode Institute)

  • Kwasi Kwakwa

    (Wellcome Genome Campus, Hinxton)

  • Eleonora Khabirova

    (Wellcome Genome Campus, Hinxton)

  • Gerda Kildisiute

    (Wellcome Genome Campus, Hinxton)

  • Thomas R. W. Oliver

    (Wellcome Genome Campus, Hinxton
    Cambridge University Hospitals NHS Foundation Trust)

  • Ronald R. Krijger

    (Princess Máxima Center for Pediatric Oncology
    University Medical Center Utrecht)

  • Marry M. Heuvel-Eibrink

    (Princess Máxima Center for Pediatric Oncology)

  • Federico Comitani

    (The Hospital for Sick Children)

  • Alice Piapi

    (UCL Great Ormond Street Hospital Institute of Child Health)

  • Eva Bugallo-Blanco

    (UCL Great Ormond Street Hospital Institute of Child Health)

  • Christine Thevanesan

    (UCL Great Ormond Street Hospital Institute of Child Health)

  • Christina Burke

    (UCL Great Ormond Street Hospital Institute of Child Health)

  • Elena Prigmore

    (Wellcome Genome Campus, Hinxton)

  • Kirsty Ambridge

    (Wellcome Genome Campus, Hinxton)

  • Kenny Roberts

    (Wellcome Genome Campus, Hinxton)

  • Felipe A. Vieira Braga

    (University of Amsterdam)

  • Tim H. H. Coorens

    (Wellcome Genome Campus, Hinxton)

  • Ignacio Valle

    (UCL Great Ormond Street Hospital Institute of Child Health)

  • Anna Wilbrey-Clark

    (Wellcome Genome Campus, Hinxton)

  • Lira Mamanova

    (Wellcome Genome Campus, Hinxton)

  • Grant D. Stewart

    (Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Vincent J. Gnanapragasam

    (Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge
    Cambridge Urology Translational Research and Clinical Trials office, Cambridge Biomedical Campus Cambridge CB2 0QQ University of Cambridge)

  • Dyanne Rampling

    (Great Ormond Street Hospital for Children NHS Foundation Trust)

  • Neil Sebire

    (NIHR Great Ormond Street Hospital BRC and Institute of Child Health)

  • Nicholas Coleman

    (Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Liz Hook

    (Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Anne Warren

    (Cambridge University Hospitals NHS Foundation Trust)

  • Muzlifah Haniffa

    (Wellcome Genome Campus, Hinxton
    Newcastle Hospitals NHS Foundation Trust
    Newcastle University)

  • Marcel Kool

    (Princess Máxima Center for Pediatric Oncology
    Hopp Children´s Cancer Center Heidelberg (KiTZ)
    Division of Pediatric Neurooncology)

  • Stefan M. Pfister

    (Hopp Children´s Cancer Center Heidelberg (KiTZ)
    Division of Pediatric Neurooncology
    Heidelberg University Hospital, Department of Pediatric Hematology and Oncology)

  • John C. Achermann

    (UCL Great Ormond Street Hospital Institute of Child Health)

  • Xiaoling He

    (University of Cambridge
    University of Cambridge)

  • Roger A. Barker

    (University of Cambridge
    University of Cambridge)

  • Adam Shlien

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

  • Omer A. Bayraktar

    (Wellcome Genome Campus, Hinxton)

  • Sarah A. Teichmann

    (Wellcome Genome Campus, Hinxton
    University of Cambridge)

  • Frank C. Holstege

    (Princess Máxima Center for Pediatric Oncology)

  • Kerstin B. Meyer

    (Wellcome Genome Campus, Hinxton)

  • Jarno Drost

    (Princess Máxima Center for Pediatric Oncology
    Oncode Institute)

  • Karin Straathof

    (UCL Great Ormond Street Hospital Institute of Child Health
    Great Ormond Street Hospital for Children NHS Foundation Trust)

  • Sam Behjati

    (Wellcome Genome Campus, Hinxton
    Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

Abstract

Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference “cellular signals” in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of “fetalness” with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer.

Suggested Citation

  • Matthew D. Young & Thomas J. Mitchell & Lars Custers & Thanasis Margaritis & Francisco Morales-Rodriguez & Kwasi Kwakwa & Eleonora Khabirova & Gerda Kildisiute & Thomas R. W. Oliver & Ronald R. Krijge, 2021. "Single cell derived mRNA signals across human kidney tumors," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23949-5
    DOI: 10.1038/s41467-021-23949-5
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    Cited by:

    1. Taryn D. Treger & John E. G. Lawrence & Nathaniel D. Anderson & Tim H. H. Coorens & Aleksandra Letunovska & Emilie Abby & Henry Lee-Six & Thomas R. W. Oliver & Reem Al-Saadi & Kjell Tullus & Guillaume, 2023. "Targetable NOTCH1 rearrangements in reninoma," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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