Neural Stem/Progenitor Cells and Progranulin

Abstract

Progranulin (PGRN) is widely expressed in the body, including the central nervous system (CNS), and controls cell growth, proliferation, differentiation, cell death, etc. In this chapter, I discuss recent findings about the roles of PGRN in neurogenesis, with a focus on its roles in neural stem and progenitor cells (NSPCs). Accumulated evidence clearly suggests that PGRN engages in neurogenesis; however, the precise mechanisms remain largely elusive. One reason is that many different cells in the CNS produce PGRN and can also react to PGRN. This produces a complex challenge to understand PGRN-dependent neurogenesis in vivo. Therefore, I initially introduce recent studies that analyze the roles of PGRN in neurogenesis. Although details about PGRN-dependent signaling in NSPCs are widely unknown, recent studies describe the physiological receptors for PGRN. The reported PGRN receptors also have binding capacities for other factors; therefore, I discuss the potential interaction between PGRN and other growth factors that control the cellular fates of NSPCs. Moreover, levels of PGRN potentially control distribution of the extracellular matrix in the CNS; conversely, the abundance of the extracellular matrix may modulate PGRN action. Therefore, the relationship between PGRN and the microenvironment, or niche, which plays a crucial role in determining the NSPC fates, is also discussed. Overall, recent studies gradually suggest that PGRN directly or indirectly influences NSPCs; however, further experiments are required to unveil the precise contribution of PGRN to neurogenesis.