Li Julia Su Zhou, Denchi Eros Lazzerini
Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Differentiation. 2018 Mar-Apr;100:21-25. doi: 10.1016/j.diff.2018.01.004. Epub 2018 Feb 2.
In multicellular organisms, regulation of telomere length in pluripotent stem cells is critical to ensure organism development and survival. Telomeres consist of repetitive DNA that are progressively lost with each cellular division. When telomeres become critically short, they activate a DNA damage response that results in cell cycle arrest. To counteract telomere attrition, pluripotent stem cells are equipped with telomere elongation mechanisms that ensure prolonged proliferation capacity and self-renewal capacity. Excessive telomere elongation can also be deleterious and is counteracted by a rapid telomere deletion mechanism termed telomere trimming. While the consequences of critically short telomeres are well established, we are only beginning to understand the mechanisms that counteract excessive telomere elongation. The balance between telomere elongation and shortening determine the telomere length set point in pluripotent stem cells and ensures sustained proliferative potential without causing chromosome instability.
在多细胞生物中，多能干细胞中端粒长度的调节对于确保生物体的发育和存活至关重要。端粒由重复性DNA组成，随着每次细胞分裂逐渐丢失。当端粒变得极短时，它们会激活DNA损伤反应，导致细胞周期停滞。为了抵消端粒磨损，多能干细胞具备端粒延长机制，以确保延长的增殖能力和自我更新能力。端粒过度延长也可能有害，一种称为端粒修剪的快速端粒缺失机制会抵消这种情况。虽然极短端粒的后果已得到充分证实，但我们才刚刚开始了解抵消端粒过度延长的机制。端粒延长和缩短之间的平衡决定了多能干细胞中的端粒长度设定点，并确保持续的增殖潜力而不引起染色体不稳定。
