title: Fractional proliferation: a method to deconvolve cell population dynamics from single-cell data.
abstract: We present an integrated method that uses extended time-lapse automated imaging to quantify the dynamics of cell proliferation. Cell counts are fit with a quiescence-growth model that estimates rates of cell division, entry into quiescence and death. The model is constrained with rates extracted experimentally from the behavior of tracked single cells over time. We visualize the output of the analysis in fractional proliferation graphs, which deconvolve dynamic proliferative responses to perturbations into the relative contributions of dividing, quiescent (nondividing) and dead cells. The method reveals that the response of 'oncogene-addicted' human cancer cells to tyrosine kinase inhibitors is a composite of altered rates of division, death and entry into quiescence, a finding that challenges the notion that such cells simply die in response to oncogene-targeted therapy.
authors.affiliation: Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. darren.tyson@vanderbilt.edu
authors.forename: Darren R
authors.initials: DR
authors.lastname: Tyson
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Garbett
authors.forename: Peter L
authors.initials: PL
authors.lastname: Frick
authors.forename: Vito
authors.initials: V
authors.lastname: Quaranta
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D002452:Cell Count; D049109:Cell Proliferation; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D018715:Microscopy, Video / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D059010:Single-Cell Analysis / Q000379:methods*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases