TY - JOUR T1 - ROS amplification drives mouse spermatogonial stem cell self-renewal JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900374 VL - 2 IS - 2 SP - e201900374 AU - Hiroko Morimoto AU - Mito Kanastu-Shinohara AU - Narumi Ogonuki AU - Satoshi Kamimura AU - Atsuo Ogura AU - Chihiro Yabe-Nishimura AU - Yoshifumi Mori AU - Takeshi Morimoto AU - Satoshi Watanabe AU - Kinya Otsu AU - Takuya Yamamoto AU - Takashi Shinohara Y1 - 2019/04/01 UR - https://www.life-science-alliance.org/content/2/2/e201900374.abstract N2 - Reactive oxygen species (ROS) play critical roles in self-renewal division for various stem cell types. However, it remains unclear how ROS 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 ROS 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 ROS levels. Chemical screening of MAPK7 targets revealed many ROS-dependent spermatogonial transcription factors, of which BCL6B was found to initiate ROS 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 ROS signals to activate ROS-dependent spermatogonial transcription factors by forming a positive feedback loop. ER -