Journal article

Intraclonal Plasticity in Mammary Tumors Revealed through Large-Scale Single-Cell Resolution 3D Imaging

Anne C Rios, Bianca D Capaldo, Francois Vaillant, Bhupinder Pal, Ravian van Ineveld, Caleb A Dawson, Yunshun Chen, Emma Nolan, Nai Yang Fu, Felicity C Jackling, Sapna Devi, David Clouston, Lachlan Whitehead, Gordon K Smyth, Scott N Mueller, Geoffrey J Lindeman, Jane E Visvader, Jamie R Flynn, William M Palmer, Antony P Martin Show all

CANCER CELL | CELL PRESS | Published : 2019

Abstract

Breast tumors are inherently heterogeneous, but the evolving cellular organization through neoplastic progression is poorly understood. Here we report a rapid, large-scale single-cell resolution 3D imaging protocol based on a one-step clearing agent that allows visualization of normal tissue architecture and entire tumors at cellular resolution. Imaging of multicolor lineage-tracing models of breast cancer targeted to either basal or luminal progenitor cells revealed profound clonal restriction during progression. Expression profiling of clones arising in Pten/Trp53-deficient tumors identified distinct molecular signatures. Strikingly, most clones harbored cells that had undergone an epithel..

View full abstract

Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by NHMRC Fellowships


Awarded by NHMRC


Funding Acknowledgements

3D Tissue Clearing and Lightsheet Microscopy Group (3DTCLSM) members: Jamie R. Flynn, William M. Palmer, Antony P. Martin, Ameha Woldu, Bill Pascoe, and Michael Nilsson. We are grateful to K. Liu for expert assistance and the WEHI Animal, Imaging, Genotyping, FACS, and Histology facilities. This work was supported by the Australian National Health and Medical Research Council (NHMRC) grant nos. 461221, 1016701, 1024852, and 1054618; NHMRC IRIISS; the Victorian State Government through VCA funding and Operational Infrastructure Support; and the Australian Cancer Research Foundation. A.C.R. and N.Y.F. were supported by a National Breast Cancer Foundation (NBCF)/Cure Cancer Australia Fellowship; P.B., G.K.S., and G.J.L. by NHMRC Fellowships nos. 1042629, 490037, and 637307; and J.E.V. by NHMRC Fellowships nos. 1037230 and 1102742.