Single-cell lineages reveal the rates, routes, and drivers of metastasis in cancer xenografts
Name
nihms-1678545.pdf
Description
Accepted version
Size
3.25 MB
Format
Unknown
Checksum (MD5)
72139751adba7fd59bac6845118870f8
Author(s)
Quinn, Jeffrey J.
Jones, Matthew G.
Okimoto, Ross A.
Nanjo, Shigeki
Chan, Michelle M.
Yosef, Nir
Bivona, Trever G.
Weissman, Jonathan S.
Date Issued
February 2021
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Version
Author's final manuscript
Abstract
Detailed phylogenies of tumor populations can recount the history and chronology of critical events during cancer progression, such as metastatic dissemination. We applied a Cas9-based, single-cell lineage tracer to study the rates, routes, and drivers of metastasis in a lung cancer xenograft mouse model. We report deeply resolved phylogenies for tens of thousands of cancer cells traced over months of growth and dissemination. This revealed stark heterogeneity in metastatic capacity, arising from preexisting and heritable differences in gene expression. We demonstrate that these identified genes can drive invasiveness and uncovered an unanticipated suppressive role for KRT17. We also show that metastases disseminated via multidirectional tissue routes and complex seeding topologies. Overall, we demonstrate the power of tracing cancer progression at subclonal resolution and vast scale.
MIT Department
Ragon Institute of MGH, MIT and Harvard
Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/science.abc1944
