TY - JOUR
T1 - Mouse spermatogenic stem cells continually interconvert between equipotent singly isolated and syncytial states
AU - Hara, Kenshiro
AU - Nakagawa, Toshinori
AU - Enomoto, Hideki
AU - Suzuki, Mikiko
AU - Yamamoto, Masayuki
AU - Simons, Benjamin D.
AU - Yoshida, Shosei
N1 - Funding Information:
We thank J. Milbrandt for providing GFRα1-EGFP and GFRα1-CreER T2 mice and J.-I. Miyazaki for providing CAG-CAT-EGFP mice. We are grateful to R. Sugimoto and K. Inada for technical instruction and assistance. We are grateful to K. Hara-Harikae, K. Ikami, Y. Kitadate, A.M. Klein, H. Mizuguchi, T. Nagasawa, Y. Nakamura, T. Ogawa, A. Philpott, M. Tokue, and E. Watanabe for useful discussions and encouragement and Y. Kuboki for secretarial assistance. We thank members of the Model Animal Research Facility of the National Institute for Basic Biology Bioresource Center for animal care. This work was partly supported by a Grant-in-Aid for Scientific Research (KAKENHI; 20116004, 24247041, and 25114004 to S.Y. and 22780267 to K.H.), Wellcome Trust (098357/Z/12/Z to B.D.S.), and the National Institutes of Natural Sciences International Exchange Program (to S.Y. and K.H.).
PY - 2014/5/1
Y1 - 2014/5/1
N2 - The identity and behavior of mouse spermatogenic stem cells have been a long-standing focus of interest. In the prevailing "As model," stem cell function is restricted to singly isolated (As) spermatogonia. By examining single-cell dynamics of GFRα1+ stem cells in vivo, we evaluate an alternative hypothesis that, through fragmentation, syncytial spermatogonia also contribute to stem cell function in homeostasis. We use live imaging and pulse labeling to quantitatively determine the fates of individual GFRα1+ cells and find that, during steady-state spermatogenesis, the entire GFRα1+ population comprises a single stem cell pool, in which cells continually interconvert between As and syncytial states. A minimal biophysical model, relying only on the rates of incomplete cell division and syncytial fragmentation, precisely predicts the stochastic fates of GFRα1+ cells during steady state and postinsult regeneration. Thus, our results define an alternative and dynamic model for spermatogenic stem cell function in the mouse testis.
AB - The identity and behavior of mouse spermatogenic stem cells have been a long-standing focus of interest. In the prevailing "As model," stem cell function is restricted to singly isolated (As) spermatogonia. By examining single-cell dynamics of GFRα1+ stem cells in vivo, we evaluate an alternative hypothesis that, through fragmentation, syncytial spermatogonia also contribute to stem cell function in homeostasis. We use live imaging and pulse labeling to quantitatively determine the fates of individual GFRα1+ cells and find that, during steady-state spermatogenesis, the entire GFRα1+ population comprises a single stem cell pool, in which cells continually interconvert between As and syncytial states. A minimal biophysical model, relying only on the rates of incomplete cell division and syncytial fragmentation, precisely predicts the stochastic fates of GFRα1+ cells during steady state and postinsult regeneration. Thus, our results define an alternative and dynamic model for spermatogenic stem cell function in the mouse testis.
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U2 - 10.1016/j.stem.2014.01.019
DO - 10.1016/j.stem.2014.01.019
M3 - Article
C2 - 24792118
AN - SCOPUS:84899712593
SN - 1934-5909
VL - 14
SP - 658
EP - 672
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 5
ER -