Genotoxic Stress Abrogates Renewal of Melanocyte Stem Cells by Triggering Their Differentiation

SummarySomatic stem cell depletion due to the accumulation of DNA damage has been implicated in the appearance of aging-related phenotypes. Hair graying, a typical sign of aging in mammals, is caused by the incomplete maintenance of melanocyte stem cells (MSCs) with age. Here, we report that irreparable DNA damage, as caused by ionizing radiation, abrogates renewal of MSCs in mice. Surprisingly, the DNA-damage response triggers MSC differentiation into mature melanocytes in the niche, rather than inducing their apoptosis or senescence. The resulting MSC depletion leads to irreversible hair graying. Furthermore, deficiency of Ataxia-telangiectasia mutated (ATM), a central transducer kinase of the DNA-damage response, sensitizes MSCs to ectopic differentiation, demonstrating that the kinase protects MSCs from their premature differentiation by functioning as a “stemness checkpoint” to maintain the stem cell quality and quantity

Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation.

金沢大学医薬保健研究域　医学系Somatic stem cell depletion due to the accumulation of DNA damage has been implicated in the appearance of aging-related phenotypes. Hair graying, a typical sign of aging in mammals, is caused by the incomplete maintenance of melanocyte stem cells (MSCs) with age. Here, we report that irreparable DNA damage, as caused by ionizing radiation, abrogates renewal of MSCs in mice. Surprisingly, the DNA-damage response triggers MSC differentiation into mature melanocytes in the niche, rather than inducing their apoptosis or senescence. The resulting MSC depletion leads to irreversible hair graying. Furthermore, deficiency of Ataxia-telangiectasia mutated (ATM), a central transducer kinase of the DNA-damage response, sensitizes MSCs to ectopic differentiation, demonstrating that the kinase protects MSCs from their premature differentiation by functioning as a "stemness checkpoint" to maintain the stem cell quality and quantity. © 2009 Elsevier Inc. All rights reserved

Experimental infection of highly and low pathogenic avian influenza viruses to chicken's, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission

Highly pathogenic avian influenza viruses (HPAIVs) have spread in both poultry and wild birds. Determining transmission routes of these viruses during an outbreak is essential for the control of avian influenza. It has been widely postulated that migratory ducks play crucial roles in the widespread dissemination of HPAIVs in poultry by carrying viruses along with their migrations; however close contacts between wild migratory ducks and poultry are less likely in modern industrial poultry farming settings. Therefore, we conducted experimental infections of HPAIVs and low pathogenic avian influenza viruses (LPAIVs) to chickens, domestic ducks, tree sparrows, jungle crows, and black rats to evaluate their roles in virus transmission. The results showed that chickens, ducks, sparrows, and crows were highly susceptible to HPAIV infection. Significant titers of virus were recovered from the sparrows and crows infected with HPAIVs, which suggests that they potentially play roles of transmission of HPAIVs to poultry. In contrast, the growth of LPAIVs was limited in each of the animals tested compared with that of HPAIVs. The present results indicate that these common synanthropes play some roles in influenza virus transmission from wild birds to poultry. (C) 2015 Elsevier B.V. All rights reserved

Hair follicle stem cells provide a functional niche for melanocyte stem cells

In most previous termstem cellnext term systems, the organization of the previous termstem cell nichenext term and the anchoring matrix required for previous termstem cellnext term maintenance are largely unknown. We report here that collagen XVII (COL17A1/BP180/BPAG2), previous termanext term hemidesmosomal transmembrane collagen, is highly expressed in previous termhair follicle stem cellsnext term (HFSCs) and is required for the maintenance not only of HFSCs but also of previous termmelanocyte stem cellsnext term (MSCs), which do not express Col17a1 but directly adhere to HFSCs. Mice lacking Col17a1 show premature previous termhairnext term graying and previous termhairnext term loss. Analysis of Col17a1-null mice revealed that COL17A1 is critical for the self-renewal of HFSCs through maintaining their quiescence and immaturity, potentially explaining the mechanism underlying previous termhairnext term loss in human COL17A1 deficiency. Moreover, forced expression of COL17A1 in basal keratinocytes, including HFSCs, in Col17a1-null mice rescues MSCs from premature differentiation and restores TGF-β signaling, demonstrating that HFSCs function as previous termanext term critical regulatory component of the MSC previous termniche.next ter