Quantifying heterogeneity and dynamics of clonal fitness in response to perturbation.

Frick PL, Paudel BB, Tyson DR, Quaranta V
J Cell Physiol. 2015 230 (7): 1403-12

PMID: 25600161 · PMCID: PMC5580929 · DOI:10.1002/jcp.24888

The dynamics of heterogeneous clonal lineages within a cell population, in aggregate, shape both normal and pathological biological processes. Studies of clonality typically relate the fitness of clones to their relative abundance, thus requiring long-term experiments and limiting conclusions about the heterogeneity of clonal fitness in response to perturbation. We present, for the first time, a method that enables a dynamic, global picture of clonal fitness within a mammalian cell population. This novel assay allows facile comparison of the structure of clonal fitness in a cell population across many perturbations. By utilizing high-throughput imaging, our methodology provides ample statistical power to define clonal fitness dynamically and to visualize the structure of perturbation-induced clonal fitness within a cell population. We envision that this technique will be a powerful tool to investigate heterogeneity in biological processes involving cell proliferation, including development and drug response.

© 2015 Wiley Periodicals, Inc.

MeSH Terms (9)

Cell Culture Techniques Cell Line Cell Proliferation Clone Cells Cycloheximide Gene Expression Regulation Genetic Fitness Humans Protein Synthesis Inhibitors

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