Neural stem cells (NSCs) are self-renewing multipotent cells that undergo symmetric and asymmetric cell division during development of the nervous system. The behavior of NSCs is tightly regulated by intrinsic processes such as transcriptional and post-transcriptional control, as well as the stem cell niche factors that activate ligand-receptor-mediated signaling pathways. However, the role of these niche factors that regulate NSC behavior is not clearly understood. We identified chondroitin sulfate proteoglycan, apolipoprotein E (ApoE) and cystatin C as factors derived from the mouse neurosphere conditioned medium. Here, we show that ApoE is an autocrine/paracrine factor that regulates NSC survival. Stimulation of NSC survival is mediated by ApoE receptor interaction and the downstream extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway. In addition, ApoE also enhanced neurosphere formation of mouse embryonic stem cell-derived NSCs. Finally, in vitro differentiation studies with ApoE knock-out NSCs suggest a role for ApoE in oligodendrogenesis.
© 2011 Institute of Medical Biology, Agency for Science and Technology Research. Journal of Neurochemistry © 2011 International Society for Neurochemistry.