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Rat spermatogonial stem cells (SSCs) choose their developmental fate by chance, independently of their surroundings, say Wu et al.
Most stem cell populations reside in a specialized “niche,” where the microenvironment keeps them from differentiating. One of the best examples is the hub of Drosophila gonads that maintains the fly's SSCs, but researchers have failed to identify a similar niche in mammalian testes. Instead, mammalian SSCs and their differentiating progeny are found side by side and experience the same environment, making it unlikely that extrinsic factors alone determine germ cell fate decisions.
Wu et al. grew rat germ cells for extended periods under homogenous conditions, and found that the cultures contained two cell types: immortal SSCs and differentiated cells that multiplied for a limited time before undergoing apoptosis. The dead cells were replaced by newly differentiated cells descended from SSCs, yet the SSCs could also self-renew, ensuring that the proportion of the two cell populations remained constant over time. Because the culture microenvironment was identical for SSC daughters that differentiated or maintained stemness, the researchers wondered whether cell fate was simply a stochastic choice made by the daughter cells themselves. Mathematical modeling indicated that the proportion of each cell type observed in the culture was consistent with stochastic fate choice if the probability of remaining an SSC was 67%.
Although the choice that a particular daughter cell makes might depend on an intrinsic determinant such as random fluctuations in gene expression, lead author Zhuoru Wu says that this doesn't preclude the cell's environment from having any influence at all. She is searching for physiological factors that might nudge cell fate in one direction or the other.