Fig. 5: Novel karyotypes frequently remain proliferative and can seed new PDTOs. | Nature Genetics

Fig. 5: Novel karyotypes frequently remain proliferative and can seed new PDTOs.

From: Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns

Fig. 5

a, CIN phenotype of PDTO-9 expressing transgenic H2B-Dendra2 during early and mature stages of outgrowth. The numbers of scored divisions are indicated in brackets. The total CIN rates were analyzed by chi-squared test (P = 0.56; not significant (NS)). b, Fate analysis of PDTO-9 progeny resulting from normal (N) or erroneous (E) cell divisions per growth stage. Alive progeny were non-proliferative until the end of the imaging window and this inactive period exceeded the average cell cycle length. The numbers of scored events are indicated in brackets. The difference in apoptotic rates was statistically significant, as determined by chi-squared test (P = 0.014 (young) and P = 0.0026 (mature)). c, As in b, but the fate analysis is shown for normal (N), chromatin bridge (CB), lagging chromatin (LC) and multipolar cell divisions (MP). d, Ratio between the cell cycle duration before a division and the progeny’s cell cycle duration (averaged) after that division. Data from young and mature PDTOs were pooled and subdivided by mitotic fidelity. The difference in cell cycle duration ratios between normal (94 branches) and erroneous divisions (76 branches) was not significant (data not normally distributed; P = 6.104 × 10−13 (Saphiro); P = 0.64 (two-sided Wilcoxon test)). In the box and whisker plots, the boxes represent quartiles 2 and 3, the horizontal lines represent median values and the whiskers represent minimum and maximum values within 1.5× the interquartile range. The data points indicate outlier values that deviate by more than 1.5× the interquartile range. e, Top: schematic of karyotype analysis of successfully formed organoids (bulk) grown from single (fit) cells derived from a parental (clonal) PDTO. Bottom: karyotype heatmaps of sequenced PDTOs (bulk; similar sized) as a proxy for the karyotype of the seeding cell. In total, 67 organoids shared the reference PDTO-9 core karyotype, seven were polyploid and five had de novo localized CNAs.

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