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

Zhuoru Wu, Katherine Luby-Phelps, Abhijit Bugde, Laura A. Molyneux, Bray Denard, Wen Hong Li, Gürol M. Süel, David L. Garbers

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)513-524
Number of pages12
JournalJournal of Cell Biology
Volume187
Issue number4
DOIs
StatePublished - Nov 16 2009

ASJC Scopus subject areas

  • Cell Biology

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