TY - JOUR
T1 - Capacity for stochastic self-renewal and differentiation in mammalian spermatogonial stem cells
AU - Wu, Zhuoru
AU - Luby-Phelps, Katherine
AU - Bugde, Abhijit
AU - Molyneux, Laura A.
AU - Denard, Bray
AU - Li, Wen Hong
AU - Süel, Gürol M.
AU - Garbers, David L.
PY - 2009/11/16
Y1 - 2009/11/16
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.200907047
DO - 10.1083/jcb.200907047
M3 - Article
C2 - 19948499
AN - SCOPUS:73349097273
SN - 0021-9525
VL - 187
SP - 513
EP - 524
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -