STAT3 Regulates Mouse Neural Progenitor Proliferation and Differentiation by Promoting Mitochondrial Metabolism

Abstract

The proliferation and differentiation of neural progenitor lay the foundation for brain development. In neural progenitors, activation of Signal Transducer and Activator of Transcription 3 (STAT3) has been found to promote proliferation and astrocytogenesis while suppressing neurogenesis. However, our study found that <i>Stat3</i> conditional knockout in neural progenitors (<i>Stat3</i> cKO) also results in increased proliferation and suppressed neurogenesis. To investigate how STAT3 regulates these processes, we attempted to identify potential STAT3 target genes by RNA-seq profiling of the control (CTL) and <i>Stat3</i> cKO neural progenitors. We found that STAT3 promotes the expression of genes involved in the mitochondrial oxidative phosphorylation (OXPHOS), and thereby promotes mitochondrial respiration and negatively regulates reactive oxygen species (ROS) production. In addition, we demonstrated that <i>Stat3</i> loss-of-function promotes proliferation via regulation of mitochondrial metabolism and downstream signaling pathways. Our study provides novel insights into the relation between STAT3, mitochondrial metabolism and the process of embryonic neurogenesis.