MRC Laboratory for Molecular Cell Biology and Department of Cell and Developmental Biology, University College London, London, United Kingdom.
Ludwig-Maximilians-University Munich, Martinsried, Germany.
Elife. 2020 Apr 7;9:e55435. doi: 10.7554/eLife.55435.
Dedifferentiation is a critical response to tissue damage, yet is not well understood, even at a basic phenomenological level. Developing cells undergo highly efficient dedifferentiation, completed by most cells within 24 hr. We use this rapid response to investigate the control features of dedifferentiation, combining single cell imaging with high temporal resolution transcriptomics. Gene expression during dedifferentiation was predominantly a simple reversal of developmental changes, with expression changes not following this pattern primarily associated with ribosome biogenesis. Mutation of genes induced early in dedifferentiation did not strongly perturb the reversal of development. This apparent robustness may arise from adaptability of cells: the relative temporal ordering of cell and molecular events was not absolute, suggesting cell programmes reach the same end using different mechanisms. In addition, although cells start from different fates, they rapidly converged on a single expression trajectory. These regulatory features may contribute to dedifferentiation responses during regeneration.
去分化是组织损伤的关键反应,但即使在基本的现象学水平上,也没有得到很好的理解。正在发育的细胞经历高度有效的去分化,大多数细胞在 24 小时内完成去分化。我们利用这种快速反应来研究去分化的控制特征,将单细胞成像与高时间分辨率转录组学结合起来。去分化过程中的基因表达主要是发育变化的简单逆转,而不符合这种模式的表达变化主要与核糖体生物发生有关。在去分化早期诱导的基因突变并没有强烈扰乱发育的逆转。这种明显的稳健性可能源于细胞的适应性:细胞和分子事件的相对时间顺序不是绝对的,这表明细胞程序使用不同的机制达到相同的终点。此外,尽管细胞从不同的命运开始,但它们很快就收敛到一个单一的表达轨迹上。这些调控特征可能有助于再生过程中的去分化反应。