SIRT1 通过促进 DNA 修复来提高人胚胎干细胞的存活率。
SIRT1 Enhances the Survival of Human Embryonic Stem Cells by Promoting DNA Repair.
机构信息
Department of Physiology and Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
Department of Biomedical Science, CHA University, Seongnam, Kyeonggido 13488, Korea.
出版信息
Stem Cell Reports. 2017 Aug 8;9(2):629-641. doi: 10.1016/j.stemcr.2017.06.001. Epub 2017 Jul 6.
Human embryonic stem cells (hESCs) hold great promise for the treatment of many incurable diseases. Sirtuin1 (SIRT1), a class III histone deacetylase, is abundantly expressed in hESCs and is known to regulate early differentiation and telomere elongation. Here, we show that downregulation of SIRT1 promotes cell death in hESCs, but not in differentiated cells, and the SIRT1-inhibition-mediated cell death is preceded by increased DNA damage. This increased DNA damage is at least partially due to decreased levels of DNA repair enzymes such as MSH2, MSH6, and APEX1. Furthermore, SIRT1 inhibition causes p53 activation, which eventually leads to DNA damage-induced apoptosis of hESCs. This study provides valuable insights into the mechanism of SIRT1-mediated hESC survival and should contribute to the development of safe and effective cell therapies.
人类胚胎干细胞（hESCs）在治疗许多无法治愈的疾病方面具有巨大的潜力。Sirtuin1（SIRT1）是一种 III 类组蛋白去乙酰化酶，在 hESCs 中大量表达，已知其可调节早期分化和端粒延长。在这里，我们表明 SIRT1 的下调会促进 hESCs 的细胞死亡，但不会促进分化细胞的死亡，并且 SIRT1 抑制介导的细胞死亡之前伴随着 DNA 损伤的增加。这种增加的 DNA 损伤至少部分归因于 DNA 修复酶如 MSH2、MSH6 和 APEX1 的水平降低。此外，SIRT1 抑制导致 p53 激活，最终导致 hESC 中由 DNA 损伤诱导的细胞凋亡。这项研究提供了对 SIRT1 介导的 hESC 存活机制的有价值的见解，应该有助于开发安全有效的细胞治疗方法。
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