RRC ID 4757
Author Zhu P, Hata R, Cao F, Gu F, Hanakawa Y, Hashimoto K, Sakanaka M.
Title Ramified microglial cells promote astrogliogenesis and maintenance of neural stem cells through activation of Stat3 function.
Journal FASEB J
Abstract The differentiation and proliferation of neural stem cells (NSCs) are regulated by a combination of their intrinsic properties (e.g., transcription factors, epigenetic factors, and microRNA regulation) and cell-extrinsic properties from the microenvironment around NSC (e.g., cytokines, growth factors, and cell-cell contact). Recently, there has been a great interest in clarifying the mechanism of the influence of the microenvironment on NSCs, especially cell-cell contact between NSCs and other types of cells nearby. In this study, we investigated whether microglial (Mi) cells influence the fate of NSCs. Coculture study showed that ramified Mi cells promoted astrogliogenesis and maintenance of NSCs through their paracrine effects. This microglia-induced astrogliogenesis was inhibited by AG490 and by overexpression of the dominant-negative form of Stat3 and SOCS3. Promoter assay revealed transactivation of Stat3 function in NSCs by Mi cells. Gene expression study revealed that mRNA of Notch family members (notch1-3) and sox9 in NSCs was significantly upregulated by Mi cells, and this up-regulation was inhibited by AG490. These results demonstrated that ramified Mi cells promoted astrogliogenesis and maintenance of NSCs by activating Stat3 function and via notch and sox9 signaling pathways.
Volume 22(11)
Pages 3866-77
Published 2008-11-1
DOI 10.1096/fj.08-105908
PII fj.08-105908
PMID 18685078
MeSH Animals Astrocytes / metabolism* Cells, Cultured Enzyme Inhibitors / pharmacology Gene Expression Regulation / drug effects Gene Expression Regulation / physiology* High Mobility Group Proteins / metabolism Microglia / metabolism* Neovascularization, Physiologic / drug effects Neovascularization, Physiologic / physiology Paracrine Communication / drug effects Paracrine Communication / physiology Rats Receptors, Notch / metabolism SOX9 Transcription Factor STAT3 Transcription Factor / metabolism* Signal Transduction / drug effects Signal Transduction / physiology* Stem Cells / metabolism* Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins / metabolism Transcription Factors / metabolism Tyrphostins / pharmacology
IF 4.966
Times Cited 33
DNA material pAxCAwt (RDB1678)