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Title: DNA repair in murine embryonic stem cells and differentiated cells

Abstract

Embryonic stem (ES) cells are rapidly proliferating, self-renewing cells that have the capacity to differentiate into all three germ layers to form the embryo proper. Since these cells are critical for embryo formation, they must have robust prophylactic mechanisms to ensure that their genomic integrity is preserved. Indeed, several studies have suggested that ES cells are hypersensitive to DNA damaging agents and readily undergo apoptosis to eliminate damaged cells from the population. Other evidence suggests that DNA damage can cause premature differentiation in these cells. Several laboratories have also begun to investigate the role of DNA repair in the maintenance of ES cell genomic integrity. It does appear that ES cells differ in their capacity to repair damaged DNA compared to differentiated cells. This minireview focuses on repair mechanisms ES cells may use to help preserve genomic integrity and compares available data regarding these mechanisms with those utilized by differentiated cells.

Authors:
 [1];  [2]
  1. Department of Cell and Cancer Biology, University of Cincinnati, Cincinnati, OH 45267 (United States), E-mail: tichyed@email.uc.edu
  2. Department of Cell and Cancer Biology, University of Cincinnati, Cincinnati, OH 45267 (United States)
Publication Date:
OSTI Identifier:
21128186
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 314; Journal Issue: 9; Other Information: DOI: 10.1016/j.yexcr.2008.02.007; PII: S0014-4827(08)00083-9; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; DNA; DNA DAMAGES; EMBRYOS; EXCISION REPAIR; NUCLEOTIDES; STEM CELLS

Citation Formats

Tichy, Elisia D., and Stambrook, Peter J. DNA repair in murine embryonic stem cells and differentiated cells. United States: N. p., 2008. Web. doi:10.1016/j.yexcr.2008.02.007.
Tichy, Elisia D., & Stambrook, Peter J. DNA repair in murine embryonic stem cells and differentiated cells. United States. doi:10.1016/j.yexcr.2008.02.007.
Tichy, Elisia D., and Stambrook, Peter J. 2008. "DNA repair in murine embryonic stem cells and differentiated cells". United States. doi:10.1016/j.yexcr.2008.02.007.
@article{osti_21128186,
title = {DNA repair in murine embryonic stem cells and differentiated cells},
author = {Tichy, Elisia D. and Stambrook, Peter J.},
abstractNote = {Embryonic stem (ES) cells are rapidly proliferating, self-renewing cells that have the capacity to differentiate into all three germ layers to form the embryo proper. Since these cells are critical for embryo formation, they must have robust prophylactic mechanisms to ensure that their genomic integrity is preserved. Indeed, several studies have suggested that ES cells are hypersensitive to DNA damaging agents and readily undergo apoptosis to eliminate damaged cells from the population. Other evidence suggests that DNA damage can cause premature differentiation in these cells. Several laboratories have also begun to investigate the role of DNA repair in the maintenance of ES cell genomic integrity. It does appear that ES cells differ in their capacity to repair damaged DNA compared to differentiated cells. This minireview focuses on repair mechanisms ES cells may use to help preserve genomic integrity and compares available data regarding these mechanisms with those utilized by differentiated cells.},
doi = {10.1016/j.yexcr.2008.02.007},
journal = {Experimental Cell Research},
number = 9,
volume = 314,
place = {United States},
year = 2008,
month = 6
}
  • Highlights: Black-Right-Pointing-Pointer hESCs and their progeny, NSCs and neurons, were exposed to ionizing radiation. Black-Right-Pointing-Pointer Upon irradiation, most hESCs died within 5-7 h. Black-Right-Pointing-Pointer Surviving NSCs underwent senescence and displayed features of astrocytes. Black-Right-Pointing-Pointer Surviving NSCs did not display the secretory phenotype expressed by pure astrocytes. Black-Right-Pointing-Pointer This study is to better understand the stress-responses of hESCs and their progeny. -- Abstract: Human embryonic stem cells (hESCs) hold promise for the treatment of many human pathologies. For example, hESCs and the neuronal stem cells (NSCs) and neurons derived from them have significant potential as transplantation therapies for a variety ofmore » neurodegenerative diseases. Two concerns about the use of hESCs and their differentiated derivatives are their ability to function and their ability to resist neoplastic transformation in response to stresses that inevitably arise during their preparation for transplantation. To begin to understand how these cells handle genotoxic stress, we examined the responses of hESCs and derived NSCs and neurons to ionizing radiation (IR). Undifferentiated hESCs were extremely sensitive to IR, with nearly all the cells undergoing cell death within 5-7 h. NSCs and neurons were substantially more resistant to IR, with neurons showing the most resistant. Of interest, NSCs that survived IR underwent cellular senescence and acquired astrocytic characteristics. Unlike IR-treated astrocytes, however, the NSC-derived astrocytic cells that survived IR did not display the typical pro-inflammatory, pro-carcinogenic senescence-associated secretory phenotype. These findings suggest distinct genotoxic stress-responses of hESCs and derived NSC and neuronal populations, and suggest that damaged NSCs, while failing to function, may not cause local inflammation.« less
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