title: Quantifying heterogeneity and dynamics of clonal fitness in response to perturbation.
abstract: 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.
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Frick
authors.forename: Bishal B
authors.initials: BB
authors.lastname: Paudel
authors.forename: Darren R
authors.initials: DR
authors.lastname: Tyson
authors.forename: Vito
authors.initials: V
authors.lastname: Quaranta
mesh_terms: D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002999:Clone Cells; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation; D056084:Genetic Fitness; D006801:Humans; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
chemical_list: D011500:Protein Synthesis Inhibitors; D003513:Cycloheximide