Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Mathematics and Computer Science, Ursinus College, Collegeville, PA, USA.
Cell Death Differ. 2023 Mar;30(3):660-672. doi: 10.1038/s41418-022-01069-x. Epub 2022 Oct 1.
Radiation exposure of healthy cells can halt cell cycle temporarily or permanently. In this work, we analyze the time evolution of p21 and p53 from two single cell datasets of retinal pigment epithelial cells exposed to several levels of radiation, and in particular, the effect of radiation on cell cycle arrest. Employing various quantification methods from signal processing, we show how p21 levels, and to a lesser extent p53 levels, dictate whether the cells are arrested in their cell cycle and how frequently these mitosis events are likely to occur. We observed that single cells exposed to the same dose of DNA damage exhibit heterogeneity in cellular outcomes and that the frequency of cell division is a more accurate monitor of cell damage rather than just radiation level. Finally, we show how heterogeneity in DNA damage signaling is manifested early in the response to radiation exposure level and has potential to predict long-term fate.
健康细胞的辐射暴露可以暂时或永久地停止细胞周期。在这项工作中，我们分析了暴露于不同辐射水平的视网膜色素上皮细胞的两个单细胞数据集的 p21 和 p53 的时间演变，特别是辐射对细胞周期阻滞的影响。我们利用信号处理的各种量化方法，展示了 p21 水平，以及在较小程度上 p53 水平，决定了细胞是否在其细胞周期中被阻滞，以及这些有丝分裂事件发生的频率有多高。我们观察到，暴露于相同剂量 DNA 损伤的单个细胞在细胞结果中表现出异质性，并且细胞分裂的频率是细胞损伤的更准确监测指标，而不仅仅是辐射水平。最后，我们展示了 DNA 损伤信号的异质性如何在早期对辐射暴露水平的反应中表现出来，并有可能预测长期命运。
