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Imaging tumour cell heterogeneity following cell transplantation into optically clear immune-deficient zebrafish

Author

Listed:
  • Qin Tang

    (Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
    Harvard Stem Cell Institute, Harvard University)

  • John C. Moore

    (Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
    Harvard Stem Cell Institute, Harvard University)

  • Myron S. Ignatius

    (Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
    Harvard Stem Cell Institute, Harvard University)

  • Inês M. Tenente

    (Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
    Harvard Stem Cell Institute, Harvard University
    Abel Salazar Biomedical Sciences Institute, University of Porto)

  • Madeline N. Hayes

    (Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
    Harvard Stem Cell Institute, Harvard University)

  • Elaine G. Garcia

    (Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
    Harvard Stem Cell Institute, Harvard University)

  • Nora Torres Yordán

    (Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
    Harvard Stem Cell Institute, Harvard University)

  • Caitlin Bourque

    (Weill Cornell Medical College
    Weill Cornell Medical College)

  • Shuning He

    (Harvard Stem Cell Institute, Harvard University
    Pediatric Oncology, Dana-Farber Cancer Institute)

  • Jessica S. Blackburn

    (Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
    Harvard Stem Cell Institute, Harvard University
    University of Kentucky)

  • A. Thomas Look

    (Harvard Stem Cell Institute, Harvard University
    Pediatric Oncology, Dana-Farber Cancer Institute)

  • Yariv Houvras

    (Weill Cornell Medical College
    Weill Cornell Medical College)

  • David M. Langenau

    (Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
    Harvard Stem Cell Institute, Harvard University)

Abstract

Cancers contain a wide diversity of cell types that are defined by differentiation states, genetic mutations and altered epigenetic programmes that impart functional diversity to individual cells. Elevated tumour cell heterogeneity is linked with progression, therapy resistance and relapse. Yet, imaging of tumour cell heterogeneity and the hallmarks of cancer has been a technical and biological challenge. Here we develop optically clear immune-compromised rag2E450fs (casper) zebrafish for optimized cell transplantation and direct visualization of fluorescently labelled cancer cells at single-cell resolution. Tumour engraftment permits dynamic imaging of neovascularization, niche partitioning of tumour-propagating cells in embryonal rhabdomyosarcoma, emergence of clonal dominance in T-cell acute lymphoblastic leukaemia and tumour evolution resulting in elevated growth and metastasis in BRAFV600E-driven melanoma. Cell transplantation approaches using optically clear immune-compromised zebrafish provide unique opportunities to uncover biology underlying cancer and to dynamically visualize cancer processes at single-cell resolution in vivo.

Suggested Citation

  • Qin Tang & John C. Moore & Myron S. Ignatius & Inês M. Tenente & Madeline N. Hayes & Elaine G. Garcia & Nora Torres Yordán & Caitlin Bourque & Shuning He & Jessica S. Blackburn & A. Thomas Look & Yari, 2016. "Imaging tumour cell heterogeneity following cell transplantation into optically clear immune-deficient zebrafish," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10358
    DOI: 10.1038/ncomms10358
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