Identification of ApoE as an autocrine/paracrine factor that stimulates neural stem cell survival via MAPK/ERK signaling pathway
Autor: | Hui Theng, Gan, Muly, Tham, Srivats, Hariharan, Srinivas, Ramasamy, Yuan Hong, Yu, Sohail, Ahmed |
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Rok vydání: | 2011 |
Předmět: |
Mice
Knockout Mitogen-Activated Protein Kinase Kinases Dose-Response Relationship Drug Cell Survival Gene Expression Regulation Developmental Cell Differentiation Embryo Mammalian Mice Inbred C57BL Mice Oligodendroglia Apolipoproteins E Prosencephalon Neural Stem Cells Animals Humans Enzyme Inhibitors Cells Cultured Low Density Lipoprotein Receptor-Related Protein-1 Protein Binding Signal Transduction |
Zdroj: | Journal of neurochemistry. 117(3) |
ISSN: | 1471-4159 |
Popis: | 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. |
Databáze: | OpenAIRE |
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