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doi:10.1083/jcb.200907047
The Journal of Cell Biology
The Rockefeller University Press, 0021-9525 $30.00
© Wu et al.
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ARTICLE

Capacity for stochastic self-renewal and differentiation in mammalian spermatogonial stem cells



Zhuoru Wu1,2, Katherine Luby-Phelps3,4, Abhijit Bugde3,4, Laura A. Molyneux1,2,6, Bray Denard1,2, Wen-Hong Li4, Gürol M. Süel2,5, and David L. Garbers1,2,6

1 Cecil H. and Ida Green Center for Reproductive Biology Sciences, 2 Department of Pharmacology, 3 Live Cell Imaging Core Facility, 4 Department of Cell Biology, 5 Green Center Division for Systems Biology, and 6 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390

Correspondence to Zhuoru Wu: zhuoru.wu{at}utsouthwestern.edu

Mammalian spermatogenesis is initiated and sustained by spermatogonial stem cells (SSCs) through self-renewal and differentiation. The basic question of whether SSCs have the potential to specify self-renewal and differentiation in a cell-autonomous manner has yet to be addressed. Here, we show that rat SSCs in ex vivo culture conditions consistently give rise to two distinct types of progeny: new SSCs and differentiating germ cells, even when they have been exposed to virtually identical microenvironments. Quantitative experimental measurements and mathematical modeling indicates that fate decision is stochastic, with constant probability. These results reveal an unexpected ability in a mammalian SSC to specify both self-renewal and differentiation through a self-directed mechanism, and further suggest that this mechanism operates according to stochastic principles. These findings provide an experimental basis for autonomous and stochastic fate choice as an alternative strategy for SSC fate bifurcation, which may also be relevant to other stem cell types.

Abbreviations used in this paper: GCS, germ cell–specific; GDNF, glial cell line–derived neurotrophic factor; MEF, mouse embryonic fibroblast; SSC, spermatogonial stem cell.

© 2009 Wu et al.
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