Abstract
The ability of hematopoietic stem cells (HSCs) to self-renew and differentiate into progenitors is essential for homeostasis of the hematopoietic system. The longevity of HSCs makes them vulnerable to accumulating DNA damage, which may be leukemogenic or result in senescence and cell death. Additionally, the ability of HSCs to self-renew and differentiate allows DNA damage to spread throughout the hematologic system, leaving the organism vulnerable to disease. In this review we discuss cell fate decisions made in the face of DNA damage and other cellular stresses, and the role of reactive oxygen species in the long-term maintenance of HSCs and their DNA damage response.
Keywords:
Ataxia-telangiectasia mutated; DNA damage; Hematopoietic stem cells; Reactive oxygen species.
© 2013.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Animals
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Ataxia Telangiectasia / genetics
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Ataxia Telangiectasia / metabolism*
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Ataxia Telangiectasia / pathology
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Ataxia Telangiectasia Mutated Proteins / genetics
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Ataxia Telangiectasia Mutated Proteins / metabolism
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BH3 Interacting Domain Death Agonist Protein / genetics
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BH3 Interacting Domain Death Agonist Protein / metabolism
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Cell Differentiation
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Cell Proliferation
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DNA Damage / genetics*
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Gene Expression Regulation
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Hematopoiesis / genetics*
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Hematopoietic Stem Cells / metabolism*
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Hematopoietic Stem Cells / pathology
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Humans
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Oxidation-Reduction
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Reactive Oxygen Species / metabolism*
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Signal Transduction
Substances
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BH3 Interacting Domain Death Agonist Protein
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BID protein, human
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Reactive Oxygen Species
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Phosphatidylinositol 3-Kinases
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Proto-Oncogene Proteins c-akt