Proliferation maintains the undifferentiated status of stem cells: The role of the planarian cell cycle regulator Cdh1
Proliferation maintains the undifferentiated status of stem cells: The role of the planarian cell cycle regulator Cdh1
复制标题
增殖维持干细胞的未分化状态：涡虫细胞周期调节因子Cdh1的作用
DOI：
10.1016/j.ydbio.2021.12.006
复制
发表时间：
2021
影响因子：
2.7
通讯作者：
Hashimoto C.
中科院分区：
文献类型：
--
作者：
Sato Y;Umesono Y;Kuroki Y;Agata K;Hashimoto C.
几十年来，细胞周期退出和分化的重合在各种干细胞和生物体中得到了描述，但由于细胞周期的复杂调控，两者之间的因果关系仍然不清楚。这里，我们使用日本涡虫，因为它们可能具有简单的细胞周期调节，其中CDH1是负责退出细胞周期的因素之一。当dh1被功能抑制时，这些浮游生物就不能维持它们的组织动态平衡，也不能再生它们缺失的身体部位。虽然cdh1基因的敲除导致干细胞显著积累，但祖细胞和分化细胞减少。进一步的分析表明，带有cdh1基因敲除的干细胞即使接受了ERK信号的激活作为诱导信号，也没有进行分化。这些结果表明，如果没有细胞周期的存在，干细胞就不可能获得分化能力。因此，我们认为，细胞周期调控决定了干细胞的分化能力，细胞周期退出G0使干细胞发生分化。
The coincidence of cell cycle exit and differentiation has been described in a wide variety of stem cells and organisms for decades, but the causal relationship is still unclear due to the complicated regulation of the cell cycle. Here, we used the planarianDugesia japonicasince they may possess a simple cell cycle regulation in which Cdh1 is one of the factors responsible for exiting the cell cycle. Whencdh1was functionally inhibited, the planarians could not maintain their tissue homeostasis and could not regenerate their missing body parts. While the knockdown ofcdh1caused pronounced accumulation of the stem cells, the progenitor and differentiated cells were decreased. Further analyses indicated that the stem cells withcdh1knockdown did not undergo differentiation even though they received ERK signaling activation as an induction signal. These results suggested that stem cells could not acquire differentiation competence without cell cycle exit. Thus, we propose that cell cycle regulation determines the differentiation competence and that cell cycle exit to G0 enables stem cells to undergo differentiation.