Nagaria Pratik, Robert Carine, Rassool Feyruz V
Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Biochim Biophys Acta. 2013 Feb;1830(2):2345-53. doi: 10.1016/j.bbagen.2012.09.001. Epub 2012 Sep 17.
Embryonic stem cells (ESCs) represent the point of origin of all cells in a given organism and must protect their genomes from both endogenous and exogenous genotoxic stress. DNA double-strand breaks (DSBs) are one of the most lethal forms of damage, and failure to adequately repair DSBs would not only compromise the ability of SCs to self-renew and differentiate, but will also lead to genomic instability and disease.
Herein, we describe the mechanisms by which ESCs respond to DSB-inducing agents such as reactive oxygen species (ROS) and ionizing radiation, compared to somatic cells. We will also discuss whether the DSB response is fully reprogrammed in induced pluripotent stem cells (iPSCs) and the role of the DNA damage response (DDR) in the reprogramming of these cells.
ESCs have distinct mechanisms to protect themselves against DSBs and oxidative stress compared to somatic cells. The response to damage and stress is crucial for the maintenance of self-renewal and differentiation capacity in SCs. iPSCs appear to reprogram some of the responses to genotoxic stress. However, it remains to be determined if iPSCs also retain some DDR characteristics of the somatic cells of origin.
The mechanisms regulating the genomic integrity in ESCs and iPSCs are critical for its safe use in regenerative medicine and may shed light on the pathways and factors that maintain genomic stability, preventing diseases such as cancer. This article is part of a Special Issue entitled Biochemistry of Stem Cells.
胚胎干细胞（ESC）代表特定生物体中所有细胞的起源点，必须保护其基因组免受内源性和外源性基因毒性应激的影响。DNA双链断裂（DSB）是最具致死性的损伤形式之一，未能充分修复DSB不仅会损害干细胞自我更新和分化的能力，还会导致基因组不稳定和疾病。
在此，我们描述了与体细胞相比，胚胎干细胞对活性氧（ROS）和电离辐射等诱导DSB的试剂作出反应的机制。我们还将讨论在诱导多能干细胞（iPSC）中DSB反应是否被完全重编程，以及DNA损伤反应（DDR）在这些细胞重编程中的作用。
与体细胞相比，胚胎干细胞具有独特的机制来保护自身免受DSB和氧化应激的影响。对损伤和应激的反应对于维持干细胞的自我更新和分化能力至关重要。诱导多能干细胞似乎对基因毒性应激的一些反应进行了重编程。然而，诱导多能干细胞是否也保留了起源体细胞的一些DDR特征仍有待确定。
调节胚胎干细胞和诱导多能干细胞基因组完整性的机制对于其在再生医学中的安全应用至关重要，可能会揭示维持基因组稳定性、预防癌症等疾病的途径和因素。本文是名为“干细胞生物化学”的特刊的一部分。
