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A role for SOX2 in the generation of microtubule-associated protein 2-positive cells from microglia

Hideki Nonaka1, Tetsuhiro Niidome, Yoriko Shinozuka

  • 1Department of Neuroscience for Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.

Biochemical and Biophysical Research Communications
|January 24, 2009
PubMed

Insights

SOX2 transcription factor drives microglia to generate microtubule-associated protein 2 (MAP2)-positive and glial fibrillary acidic protein (GFAP)-positive cells. This process involves SMAD4, highlighting SOX2

Area of Science:

  • Neuroscience
  • Stem Cell Biology
  • Molecular Biology

Background:

  • Microglia, a type of multipotential stem cell, can differentiate into microtubule-associated protein 2 (MAP2)-positive and glial fibrillary acidic protein (GFAP)-positive cells.
  • The transcription factor SOX2 is crucial in stem cell differentiation and development.

Purpose of the Study:

  • To investigate the role of SOX2 in the generation of MAP2-positive and GFAP-positive cells from microglia.
  • To elucidate the molecular mechanisms underlying SOX2-mediated differentiation of microglia.

Main Methods:

  • Western blot analysis to assess SOX2 expression levels.
  • Immunocytochemical analyses to detect SOX2 localization and cell differentiation markers (MAP2, GFAP).
  • Small interfering RNA (siRNA) knockdown of SOX2 and SMAD4 to evaluate their functional roles.

Main Results:

  • Fetal bovine serum treatment upregulated SOX2 expression in microglia.
  • SOX2 was detected in the nuclei of differentiated microglia (MAP2-positive, GFAP-positive cells) but not in parent microglia.
  • Knockdown of SOX2 or SMAD4 using siRNA inhibited the generation of MAP2-positive and GFAP-positive cells from microglia.
  • SMAD4 knockdown reduced SOX2 expression, suggesting its involvement in SOX2 regulation.

Conclusions:

  • SOX2 upregulation is critical for the differentiation of microglia into MAP2-positive and GFAP-positive cells.
  • The SMAD4 pathway is involved in regulating SOX2 expression and subsequent microglial differentiation.
  • These findings reveal a novel mechanism of microglial plasticity mediated by SOX2 and SMAD4.

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