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Updated: Jun 19, 2026
Engineering of Human Blood-Induced Microglia-like Cells for Reverse-Translational Brain Research
Published on: September 6, 2024
Basic fibroblast growth factor promotes the generation of microtubule-associated protein 2-positive cells from
Tetsuhiro Niidome1, Hideki Nonaka, Akinori Akaike
1Department of Neuroscience for Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan. tniidome@pharm.kyoto-u.ac.jp
Abstract:
We recently demonstrated that microglia as multipotential stem cells give rise to microtubule-associated protein 2 (MAP2)-positive and glial fibrillary acidic protein (GFAP)-positive cells and that microglia-derived MAP2-positive cells possess properties of functional neurons. In this study, we investigated the role of fibroblast growth factor (FGF) signaling in the molecular mechanism underlying the generation of microglia-derived MAP2-positive and GFAP-positive cells. Real-time quantitative PCR analyses demonstrated that mRNA levels of a family of three FGF receptors, Fgfr1-3, were upregulated in microglia treated with 70% fetal bovine serum (FBS). Immunocytochemical analyses demonstrated that basic FGF (bFGF) promoted the generation of microglia-derived MAP2-positive and GFAP-positive cells, and the FGF receptor tyrosine kinase inhibitor SU5402 and the MEK inhibitor PD98059 both inhibited this process. Western blot analyses demonstrated that bFGF increased phosphorylated ERK1/2 levels without altering total ERK1/2 levels. These results suggest that bFGF promotes the generation of microglia-derived MAP2-positive and GFAP-positive cells via FGF receptors and the ERK-MAP kinase pathway.
Insights
Fibroblast growth factor (FGF) signaling drives microglia stem cells to become neuron-like cells. This process involves FGF receptors and the ERK-MAP kinase pathway, revealing a novel mechanism for cell differentiation.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Molecular Biology
Background:
- Microglia, immune cells in the brain, have been shown to act as multipotent stem cells.
- These microglia can differentiate into cells expressing neuronal markers (MAP2) and astrocyte markers (GFAP).
- The molecular mechanisms regulating this microglia differentiation remain largely unexplored.
Purpose of the Study:
- To investigate the role of fibroblast growth factor (FGF) signaling in microglia differentiation.
- To elucidate the molecular pathways involved in the generation of microglia-derived MAP2-positive and GFAP-positive cells.
Main Methods:
- Real-time quantitative PCR to analyze FGF receptor (Fgfr1-3) mRNA expression in microglia.
- Immunocytochemistry to assess the effects of basic FGF (bFGF) and inhibitors on cell differentiation.
- Western blot analysis to examine the activation of the ERK-MAP kinase pathway (phosphorylated ERK1/2).
Main Results:
- FGF receptor mRNA levels (Fgfr1-3) were upregulated in microglia treated with fetal bovine serum (FBS).
- Basic FGF (bFGF) treatment promoted the generation of microglia-derived MAP2-positive and GFAP-positive cells.
- Inhibition of FGF receptor tyrosine kinase (SU5402) and MEK (PD98059) suppressed bFGF-induced differentiation.
- bFGF treatment led to increased phosphorylation of ERK1/2, indicating activation of the ERK-MAP kinase pathway.
Conclusions:
- Basic FGF (bFGF) signaling is a key regulator in the differentiation of microglia into neuronal and glial-like cells.
- The FGF receptor and downstream ERK-MAP kinase pathway mediate bFGF's pro-differentiation effects on microglia.
- These findings highlight a novel mechanism by which microglia can generate functional neuronal and glial cells.
