Figure 5
From: p53 dynamics in single cells are temperature-sensitive
The p53 response to hyperthermia is reversible (A) Cells pre-equilibrated at 41 °C (see Fig. 2) were tracked for 48 h. After 6 h, temperature was reduced to 37 °C. We observed immediate decreases in p53 levels followed by pulsatile dynamics. Median p53 levels of cell populations are indicated. See Table S1 for number of analysed cells. The lower graph indicates corresponding cumulative fractions of cells dividing over time. (B) Quantification of amplitudes for the first 6 pulses detected by the dynamic time warping approach for cell populations shown in (A). The first feature corresponds to the acute p53 response to hyperthermia. Subsequent pulses mainly detected after reducing the temperature do not differ among irradiated (open boxes) and non-irradiated cells (solid boxes). Red lines indicate medians of distributions; boxes include data between the 25th and 75th percentiles; whiskers extend to maximum values within 1.5 × the interquartile range. Estimated changes between irradiated and non-irradiated cells are indicated below (red dots); error bars represent 95% confidence intervals determined by permutation testing. Dashed lines serve as guides to the eye. (C–D) Heatmap of normalized p53 levels for the non-irradiated (C) and irradiated (D) cell population sorted by the position of the first new feature appearing after the temperature was set to 37 °C (6 h). The data shown was adjusted using images processing techniques to enhance visualization of pulsatile dynamics (see methods section). (E) Probabilities of being in a certain feature at a given time point for irradiated and non-irradiated cells. The induced pulsing is less heterogeneous for irradiated cells. Non-irradiated cells have on average less pulses.
