Fig. 1: Segregation error frequencies of chromosomes during error-prone mitosis are non-random.

a, Representative still images of synchronous RPE1-hTERT H2B-mNeon cells undergoing mitosis in the presence of Cpd-5. Arrowheads indicate mis-segregating chromosomes (scale bars, 5 μm). b,c, Representative replication (b) and quantification (c) showing the copy number states of synchronised RPE1-hTERT cells treated with DMSO or Cpd-5. Each row represents one nucleus, and different colours represent copy number states. The graph shows aneuploidy percentages per chromosome for three independent experiments (mean ± s.e.m., two-tailed binomial test, n = 410 aneuploid cells). Different colours denote whether the chromosome has been lost, gained or partially lost or gained. The horizontal black line at 4.34% depicts the expected random chance of mis-segregation of each chromosome. Numbers at the top of columns in c are P values. d,e, Representative FISH image (d) and quantification (e) of RPE1-hTERT cells as treated in b but fixed 45 min after release from RO-3306 (scale bar, 5 μm). Arrowhead indicates a lagging chromosome 2. The graph plots the percentage of chromosomes positive for corresponding FISH probes on the y axis versus the aneuploidy percentages determined in c (mean ± s.e.m., two-tailed Pearson's correlation coefficient; chr1, n = 327; chr2, n = 307; chr4, n = 311; chr6, n = 290; chr10, n = 322; chr11, n = 313; chr15, n = 286; chrX, n = 314). Three independent experiments were performed. f, Representative still images of human intestinal organoids treated with either DMSO as a control or the Aurora B inhibitor ZM447439 (scale bars, 5 μm). Arrowheads indicate mis-segregating chromosomes. g, Plot comparing aneuploidy percentages of human intestinal organoids after overnight Cpd-5 versus ZM447439 treatment (mean ± s.e.m., two-tailed Pearson's correlation coefficient, n = 217 and n = 64 aneuploid cells, respectively). The experiment was performed in duplicate.