| First Author | Rios AC | Year | 2019 |
| Journal | Cancer Cell | Volume | 35 |
| Issue | 4 | Pages | 618-632.e6 |
| PubMed ID | 30930118 | Mgi Jnum | J:274188 |
| Mgi Id | MGI:6295031 | Doi | 10.1016/j.ccell.2019.02.010 |
| Citation | Rios AC, et al. (2019) Intraclonal Plasticity in Mammary Tumors Revealed through Large-Scale Single-Cell Resolution 3D Imaging. Cancer Cell 35(4):618-632.e6 |
| abstractText | 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 epithelial-to-mesenchymal transition, indicating widespread, inherent plasticity. Hence, an integrative pipeline that combines lineage tracing, 3D imaging, and clonal RNA sequencing technologies offers a comprehensive path for studying mechanisms underlying heterogeneity in whole tumors. |
