The hypoxia-inducible factor EPAS1 is required for normal spermatogonial stem cell function in regenerative conditions [Dstat bulkRNAseq]

In this study we explored the role of hypoxia and the hypoxia-inducible transcription factor EPAS1 in regulating spermatogonial stem cell (SSC) function in the mouse. We demonstrated that SSCs reside in hypoxic microenvironments in the testis through utilisation of the oxygen-sensing probe pimonidazole, and by confirming the stable presence of EPAS1, which is degraded at >5% O2. Here we stabilised EPAS1 expression in primary cultures of undifferentiated spermatogonia with the small drug molecule Daprodustat, providing a platform to identify genes whose expression is regulated by EPAS1 in SSCs. Four biological replicates for each treatment (vehicle control or Daprodustat)