College of Life Science and Technology, Huazhong Agricultural University, Wuhan, P.R. China.
Key Laboratory of Horticultural Plant Biology (Ministry of Education), Huazhong Agricultural University, Wuhan, P.R. China.
Nat Plants. 2020 Sep;6(9):1098-1105. doi: 10.1038/s41477-020-0745-9. Epub 2020 Aug 17.
DNA damage can result from intrinsic cellular processes and from exposure to stressful environments. Such DNA damage generally threatens genome integrity and cell viability. However, here we report that the transient induction of DNA strand breaks (single-strand breaks, double-strand breaks or both) in the moss Physcomitrella patens can trigger the reprogramming of differentiated leaf cells into stem cells without cell death. After intact leafy shoots (gametophores) were exposed to zeocin, an inducer of DNA strand breaks, the STEM CELL-INDUCING FACTOR 1 (STEMIN1) promoter was activated in some leaf cells. These cells subsequently initiated tip growth and underwent asymmetric cell divisions to form chloronema apical stem cells, which are in an earlier phase of the life cycle than leaf cells and have the ability to form new gametophores. This DNA-strand-break-induced reprogramming required the DNA damage sensor ATR kinase, but not ATM kinase, together with STEMIN1 and closely related proteins. ATR was also indispensable for the induction of STEMIN1 by DNA strand breaks. Our findings indicate that DNA strand breaks, which are usually considered to pose a severe threat to cells, trigger cellular reprogramming towards stem cells via the activity of ATR and STEMINs.
DNA 损伤可能来自细胞内部过程，也可能来自于暴露在压力环境中。这种 DNA 损伤通常会威胁到基因组的完整性和细胞活力。然而，在这里我们报告说，在藓类植物Physcomitrella patens 中短暂诱导 DNA 链断裂（单链断裂、双链断裂或两者兼有）可以触发已分化的叶细胞向干细胞的重新编程，而不会导致细胞死亡。在完整的有叶芽（配子体）暴露于 zeocin （一种诱导 DNA 链断裂的试剂）后，STEM CELL-INDUCING FACTOR 1（STEMIN1）启动子在一些叶细胞中被激活。这些细胞随后开始顶端生长，并经历不对称细胞分裂，形成原丝体顶端干细胞，这些细胞处于生命周期的早期阶段，比叶细胞具有形成新配子体的能力。这种 DNA 链断裂诱导的重编程需要 DNA 损伤传感器 ATR 激酶，但不需要 ATM 激酶，以及 STEMIN1 和密切相关的蛋白质。ATR 对于 DNA 链断裂诱导 STEMIN1 的表达也是必不可少的。我们的研究结果表明，通常被认为对细胞构成严重威胁的 DNA 链断裂，通过 ATR 和 STEMINs 的活性，触发了细胞向干细胞的重新编程。
