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

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, Yariv Houvras and David M. Langenau ()
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Qin Tang: Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
John C. Moore: Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
Myron S. Ignatius: Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
Inês M. Tenente: Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
Madeline N. Hayes: Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
Elaine G. Garcia: Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
Nora Torres Yordán: Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
Caitlin Bourque: Weill Cornell Medical College
Shuning He: Harvard Stem Cell Institute, Harvard University
Jessica S. Blackburn: Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital
A. Thomas Look: Harvard Stem Cell Institute, Harvard University
Yariv Houvras: Weill Cornell Medical College
David M. Langenau: Molecular Pathology, Cancer Center, and Regenerative Medicine, Massachusetts General Hospital

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10358

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