Stem Cell Defects in ATM-Deficient Undifferentiated Spermatogonia through DNA Damage-Induced Cell-Cycle Arrest

Keiyo Takubo, Masako Ohmura, Masaki Azuma, Go Nagamatsu, Wakako Yamada, Fumio Arai, Atsushi Hirao, Toshio Suda

研究成果: Contribution to journalArticle査読

99 被引用数 (Scopus)

抄録

Mammalian spermatogenesis is maintained by stem cell capacity within undifferentiated spermatogonial subpopulation. Here, using a combination of surface markers, we describe a purification method for undifferentiated spermatogonia. Flow cytometric analysis revealed that this population is composed of Plzf-positive cells and exhibits quiescence and the side population phenotype, fulfilling general stem cell criteria. We then applied this method to analyze undifferentiated spermatogonia and stem cell activity of Atm-/- mice. Atm-/- testis shows progressive depletion of undifferentiated spermatogonia accompanied by cell-cycle arrest. In Atm-/- undifferentiated spermatogonia, a self-renewal defect was observed in vitro and in vivo. Accumulation of DNA damage and activation of the p19Arf-p53-p21Cip1/Waf1 pathway were observed in Atm-/- undifferentiated spermatogonia. Moreover, suppression of p21Cip1/Waf1 in an Atm-/- background restored transplantation ability of undifferentiated spermatogonia, indicating that ATM plays an essential role in maintenance of undifferentiated spermatogonia and their stem cell capacity by suppressing DNA damage-induced cell-cycle arrest.

本文言語英語
ページ(範囲)170-182
ページ数13
ジャーナルCell stem cell
2
2
DOI
出版ステータス出版済み - 2 7 2008
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 遺伝学
  • 細胞生物学

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