Role of Fanconi DNA repair pathway in neural stem cell homeostasis.
Defects in DNA repair pathways have been involved in collapse of early neurogenesis leading to brain development abnormalities and embryonic lethality. However, consequences of DNA repair defects in adult neural stem and progenitor cells and their potential contribution in ageing phenotype are poorly understood. The Fanconi anaemia (FA) pathway, which functions primarily as a DNA damage response system, has been examined in neural stem and progenitor cells during developmental and adult neurogenesis. We have shown that loss of fanca and fancg specifically provokes neural progenitor apoptosis during forebrain development, related to DNA repair defects, which persists in adulthood leading to depletion of the neural stem cell pool with ageing. In addition, neural stem cells from FA mice had a reduced capacity to self-renew in vitro. Here, we expand upon our recent work and give further data examining possible implication of oxidative stress. Therefore, FA phenotype might be interpreted as a premature ageing of stem cells, DNA damages being among the driving forces of ageing.
Sii-Felice
Karine
K
CEA, DSV, iRCM, SCSR, Laboratoire de Radiopathologie, Fontenay-aux-Roses, France.
Barroca
Vilma
V
Etienne
Olivier
O
Riou
Lydia
L
Hoffschir
Françoise
F
Fouchet
Pierre
P
Boussin
François D
FD
Mouthon
Marc-André
MA
D000375:Aging / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D004249:DNA Damage; D004260:DNA Repair; D005199:Fanconi Anemia / Q000378:metabolism*; D052217:Fanconi Anemia Complementation Group A Protein / Q000378:metabolism*; D052241:Fanconi Anemia Complementation Group G Protein / Q000378:metabolism*; D006706:Homeostasis; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress; D013234:Stem Cells / Q000378:metabolism*
D052217:Fanconi Anemia Complementation Group A Protein; D052241:Fanconi Anemia Complementation Group G Protein