title: Transgenerational cell fate profiling: a method for the graphical presentation of complex cell cycle alterations.
abstract: The illicit generation of tetraploid cells constitutes a prominent driver of oncogenesis, as it often precedes the development of aneuploidy and genomic instability. In addition, tetraploid (pre-)malignant cells display an elevated resistance against radio- and chemotherapy. Here, we report a strategy to preferentially kill tetraploid tumor cells based on the broad-spectrum kinase inhibitor SP600125. Live videomicroscopy revealed that SP600125 affects the execution of mitosis, impedes proper cell division and/or activates apoptosis in near-to-tetraploid, though less so in parental, cancer cells. We propose a novel graphical model to quantify the differential response of diploid and tetraploid cells to mitotic perturbators, including SP600125, which we baptized "transgenerational cell fate profiling." We speculate that this representation constitutes a valid alternative to classical "single-cell fate" and "genealogical" profiling and, hence, may facilitate the analysis of cell fate within a heterogeneous population as well as the visual examination of cell cycle alterations.
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Jemaà
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.forename: Maria
authors.initials: M
authors.lastname: Castedo
authors.forename: Santiago
authors.initials: S
authors.lastname: Rello-Varona
authors.forename: Ilio
authors.initials: I
authors.lastname: Vitale
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000873:Anthracenes / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D004171:Diploidy; D045325:HCT116 Cells; D006801:Humans; D018715:Microscopy, Video; D047428:Protein Kinase Inhibitors / Q000633:toxicity*; D057891:Tetraploidy; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D000873:Anthracenes; D047428:Protein Kinase Inhibitors; D016159:Tumor Suppressor Protein p53; C432165:pyrazolanthrone