ROS amplification drives mouse spermatogonial stem cell self-renewal.

Reactive oxygen species play critical roles in self-renewal division for various stem cell types. However, it remains unclear how signals are integrated with self-renewal machinery. Here, we report that the MAPK14/MAPK7/BCL6B pathway creates a positive feedback loop to drive spermatogonial stem cell (SSC) self-renewal via duanyu1670 amplification. The activation of MAPK14 induced MAPK7 phosphorylation in cultured SSCs, and targeted deletion of Mapk14 or Mapk7 resulted in significant SSC deficiency after spermatogonial transplantation. The activation of this signaling pathway not only induced Nox1 but also increased duanyu1670 levels. Chemical screening of MAPK7 targets revealed many spermatogonial transcription factors, of which BCL6B was found to initiate duanyu1670 production by increasing Nox1 expression via ETV5-induced nuclear translocation. Because hydrogen peroxide or Nox1 transfection also induced BCL6B nuclear translocation, our results suggest that BCL6B initiates and amplifies duanyu1670 signals to activate duanyu1670-dependent spermatogonial transcription factors by forming a positive feedback loop.

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