title: Identification of ApoE as an autocrine/paracrine factor that stimulates neural stem cell survival via MAPK/ERK signaling pathway.
abstract: 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.
authors.affiliation: Neural Stem Cell Laboratory, Institute of Medical Biology, Singapore.
authors.forename: Hui Theng
authors.initials: HT
authors.lastname: Gan
authors.forename: Muly
authors.initials: M
authors.lastname: Tham
authors.forename: Srivats
authors.initials: S
authors.lastname: Hariharan
authors.forename: Srinivas
authors.initials: S
authors.lastname: Ramasamy
authors.forename: Yuan Hong
authors.initials: YH
authors.lastname: Yu
authors.forename: Sohail
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D009836:Oligodendroglia / Q000502:physiology; D016548:Prosencephalon / Q000166:cytology; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D001057:Apolipoproteins E; D004791:Enzyme Inhibitors; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D020929:Mitogen-Activated Protein Kinase Kinases