Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 170-182 |
| Number of pages | 13 |
| Journal | Cell Stem Cell |
| Volume | 2 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2008 Feb 7 |
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Keywords
- STEMCELL
ASJC Scopus subject areas
- Cell Biology
- Molecular Medicine
- Genetics
Cite this
Stem Cell Defects in ATM-Deficient Undifferentiated Spermatogonia through DNA Damage-Induced Cell-Cycle Arrest. / Takubo, Keiyo; Ohmura, Masako; Azuma, Masaki; Nagamatsu, Go; Yamasawa, Wakako; Arai, Fumio; Hirao, Atsushi; Suda, Toshio.
In: Cell Stem Cell, Vol. 2, No. 2, 07.02.2008, p. 170-182.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Stem Cell Defects in ATM-Deficient Undifferentiated Spermatogonia through DNA Damage-Induced Cell-Cycle Arrest
AU - Takubo, Keiyo
AU - Ohmura, Masako
AU - Azuma, Masaki
AU - Nagamatsu, Go
AU - Yamasawa, Wakako
AU - Arai, Fumio
AU - Hirao, Atsushi
AU - Suda, Toshio
PY - 2008/2/7
Y1 - 2008/2/7
N2 - 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.
AB - 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.
KW - STEMCELL
UR - http://www.scopus.com/inward/record.url?scp=38649099103&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38649099103&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2007.10.023
DO - 10.1016/j.stem.2007.10.023
M3 - Article
C2 - 18371438
AN - SCOPUS:38649099103
VL - 2
SP - 170
EP - 182
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 2
ER -