Capacity for stochastic self-renewal and differentiation in mammalian spermatogonial stem cells.
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.
Wu
Zhuoru
Z
Cecil H. and Ida Green Center for Reproductive Biology Sciences, Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. zhuoru.wu@utsouthwestern.edu
Luby-Phelps
Katherine
K
Bugde
Abhijit
A
Molyneux
Laura A
LA
Denard
Bray
B
Li
Wen-Hong
WH
Süel
Gürol M
GM
Garbers
David L
DL
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D003198:Computer Simulation; D017124:Conserved Sequence; D045604:Extracellular Fluid / Q000166:cytology / Q000502:physiology; D005854:Germ Cells / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D013093:Spermatogonia / Q000166:cytology* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D013269:Stochastic Processes