title: Ionizing radiation leads to the replacement and de novo production of colonic Lgr5(+) stem cells.
abstract: Tissue stem cells have self-renewal capability throughout their whole life, which is high enough to lead to the accumulation of DNA damage in a stem cell pool. Whether radiation-induced damage accumulates in tissue stem cells remains unknown, but could be investigated if the fate of tissue stem cells could be followed after irradiation. To realize this goal, we used an Lgr5-dependent lineage tracing system that allows the conditional in vivo labeling of Lgr5(+) intestinal stem cells and their progeny. We found that radiation induced loss of Lgr5(+) stem cells in the colon, but not in the duodenum. Interestingly, the loss of colonic Lgr5(+) cells was compensated by de novo production of Lgr5(+) cells, which increased after irradiation. These findings show that ionizing radiation effectively stimulates the turnover of colonic Lgr5(+) stem cells, implying that radiation-induced damage does not accumulate in the colonic Lgr5(+) stem cells by this mechanism.
authors.affiliation: Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry, Komae, Tokyo, Japan. ohken@criepi.denken.or.jp
authors.forename: Kensuke
authors.initials: K
authors.lastname: Otsuka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamada
authors.forename: Junji
authors.initials: J
authors.lastname: Magae
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hoshi
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D019070:Cell Lineage / Q000528:radiation effects; D003106:Colon / Q000166:cytology*; D051379:Mice; D009928:Organ Specificity; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*
chemical_list: C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled