Ramified microglial cells promote astrogliogenesis and maintenance of neural stem cells through activation of Stat3 function

Pengxiang Zhu, Ryuji Hata, Fang Cao, Feng Gu, Yasushi Hanakawa, Koji Hashimoto, Masahiro Sakanaka

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3866-3877
Number of pages12
JournalFASEB Journal
Volume22
Issue number11
DOIs
Publication statusPublished - 01-11-2008

Fingerprint

Neural Stem Cells
Stem cells
Chemical activation
Maintenance
MicroRNAs
Gene expression
Microglia
Assays
Coculture Techniques
Intercellular Signaling Peptides and Proteins
Transcription Factors
Epigenomics
Transcriptional Activation
Cytokines
Up-Regulation
Messenger RNA
Gene Expression

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Zhu, Pengxiang ; Hata, Ryuji ; Cao, Fang ; Gu, Feng ; Hanakawa, Yasushi ; Hashimoto, Koji ; Sakanaka, Masahiro. / Ramified microglial cells promote astrogliogenesis and maintenance of neural stem cells through activation of Stat3 function. In: FASEB Journal. 2008 ; Vol. 22, No. 11. pp. 3866-3877.
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Ramified microglial cells promote astrogliogenesis and maintenance of neural stem cells through activation of Stat3 function. / Zhu, Pengxiang; Hata, Ryuji; Cao, Fang; Gu, Feng; Hanakawa, Yasushi; Hashimoto, Koji; Sakanaka, Masahiro.

In: FASEB Journal, Vol. 22, No. 11, 01.11.2008, p. 3866-3877.

Research output: Contribution to journalArticle

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