Expression of signal transducers and activator of transcription 3 (STAT3) determines differentiation of olfactory bulb cells

Abstract

Signal transducers and activator of transcription (STAT) proteins are activated in response to many cytokines and growth factors. Many studies indicated that regulation of STAT expression plays an important role in survival, growth, and differentiation of neurons and glias in response to ciliary neurotropic factor, including rehabilitation of rat cortical injury, nerve regeneration, gangliosides-mediated stimulation of rat and murine primary microglia, and differentiation of retinal neurons. In this study, we use olfactory bulb neurons as a useful model, which undergo strong neurogenesis throughout adulthood. Our research demonstrated that low level of STAT3 expression facilitates the terminal differentiation of olfactory bulb neurons as well as induces the generation of neurons from neural stem cells, which can be potentially used in future therapies. On the contrary, activation of STAT3 expression is essential to the maintenance of stem-like status in olfactory cells. This activation can be manipulated by leukemia inhibitory factor (LIF), a member of cytosolic tyrosine kinases. All these results implicate that STAT3 serves as a critical protein in regulating the differentiation state in neural cells.