title: Regulation of reactive oxygen species and genomic stability in hematopoietic stem cells.
abstract: Hematopoietic stem cells (HSCs) are defined by their ability both to self-renew and to give rise to fresh blood cells throughout the lifetime of an animal. The failure of HSCs to self-renew during aging is believed to depend on several intrinsic (cell-autonomous) and extrinsic (non-cell-autonomous) factors. In this review, we focus on how dysregulation of reactive oxygen species (ROS) and disruptions of genomic stability can impair HSC functions. Recently, it was shown that long-term self-renewing HSCs normally possess low levels of intracellular ROS. However, when intracellular ROS levels become excessive, they cause senescence or apoptosis, resulting in a failure of HSC self-renewal. Repression of intracellular ROS levels in HSCs by treatment with an antioxidant that scavenges ROS can rescue HSC functions, indicating that excess ROS levels are at the root of HSC failure. Products of numerous genes that are involved in either DNA-damage responses or longevity-related signaling contribute to the maintenance of the HSC self-renewal capacity. Further investigations on the molecular mechanisms of ROS regulation and on the manipulation of excess ROS levels could lead to the development of novel therapeutics for hematopoietic diseases, regenerative medicine, and the prevention of leukemia.
authors.affiliation: Division of Molecular Genetics, Center for Cancer and Stem Cell Research, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Naka
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Muraguchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hoshii
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirao
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D004249:DNA Damage; D042822:Genomic Instability; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D016615:Telomere / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species