RRC ID 57374
Author Morimoto H, Kanastu-Shinohara M, Ogonuki N, Kamimura S, Ogura A, Yabe-Nishimura C, Mori Y, Morimoto T, Watanabe S, Otsu K, Yamamoto T, Shinohara T.
Title ROS amplification drives mouse spermatogonial stem cell self-renewal.
Journal Life Sci Alliance
Abstract 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.
Volume 2(2)
Published 2019-4-1
DOI 10.26508/lsa.201900374
PII 2/2/e201900374
PMID 30940732
PMC PMC6448598
MeSH Adult Germline Stem Cells / physiology* Animals Benzodiazepinones / pharmacology Cell Proliferation / drug effects Cell Self Renewal / physiology* DNA-Binding Proteins / metabolism Feedback, Physiological / physiology Gene Knockout Techniques Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Knockout Mitogen-Activated Protein Kinase 14 / genetics Mitogen-Activated Protein Kinase 14 / metabolism Mitogen-Activated Protein Kinase 7 / genetics Mitogen-Activated Protein Kinase 7 / metabolism NADPH Oxidase 1 / genetics NADPH Oxidase 1 / metabolism Reactive Oxygen Species / metabolism* Real-Time Polymerase Chain Reaction Repressor Proteins / genetics Repressor Proteins / metabolism Transcription Factors / genetics Transcription Factors / metabolism Transfection
Times Cited 2
Resource
DNA material AxCANLacZ (RDB01749) AxCANCre (RDB01748)