Impact of the hypoxic microenvironment on spermatogonial stem cells in culture
Résumé
The stem cell niche plays a crucial role in the decision to either self-renew or differentiate. Recent observations lead to the hypothesis that O 2 supply by blood and local O 2 tension could be key components of the testicular niche of spermatogonial stem cells (SSCs). In this study, we investigated the impact of different hypoxic conditions (3.5%, 1%, and 0.1% O 2 tension) on murine and human SSCs in culture. We observed a deleterious effect of severe hypoxia (1% O 2 and 0.1% O 2 ) on the capacity of murine SSCs to form germ cell clusters when plated at low density. Severe effects on SSCs proliferation occur at an O 2 tension ≤1% and hypoxia was shown to induce a slight differentiation bias under 1% and 0.1% O 2 conditions. Exposure to hypoxia did not appear to change the mitochondrial mass and the potential of membrane of mitochondria in SSCs, but induced the generation of mitochondrial ROS at 3.5% and 1% O 2 . In 3.5% O 2 conditions, the capacity of SSCs to form colonies was maintained at the level of 21% O 2 at low cell density, but it was impossible to amplify and maintain stem cell number in high cell density culture. In addition, we observed that 3.5% hypoxia did not improve the maintenance and propagation of human SSCs. Finally, our data tend to show that the transcription factors HIF-1α and HIF-2α are not involved in the SSCs cell autonomous response to hypoxia.
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Licence : CC BY - Paternité
Licence : CC BY - Paternité