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Updated: May 26, 2026

Generation of Human Neurons and Oligodendrocytes from Pluripotent Stem Cells for Modeling Neuron-Oligodendrocyte Interactions
Published on: November 9, 2020
Sema4D as an inhibitory regulator in oligodendrocyte development
Wataru Yamaguchi1, Rie Tamai, Miho Kageura
1Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. wa-ta-ru@sahs.med.osaka-u.ac.jp
Semaphorin 4D (Sema4D) inhibits oligodendrocyte differentiation by promoting cell death. Reducing Sema4D increases oligodendrocyte numbers, while adding Sema4D enhances cell death, revealing its role in development.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- The intrinsic regulation of oligodendrocyte (OL) differentiation is not fully understood.
- Oligodendrocytes express Semaphorin 4D (Sema4D), a protein previously linked to axon guidance.
- Previous studies suggest Sema4D influences oligodendrocyte development.
Purpose of the Study:
- To investigate the role of Sema4D in oligodendrocyte differentiation.
- To determine the effects of Sema4D deficiency and exogenous Sema4D on OL development.
Main Methods:
- Assessed oligodendrocyte numbers in Sema4D-deficient mice at various postnatal ages.
- Examined proliferation and apoptosis of OL progenitor cells in vivo and in vitro.
- Administered exogenous Sema4D to cultured oligodendrocytes.
Main Results:
- Sema4D deficiency increased oligodendrocyte numbers without affecting progenitor proliferation.
- Reduced apoptosis of oligodendrocytes was observed in Sema4D-deficient mice and cultures.
- Exogenous Sema4D increased oligodendrocyte apoptosis.
Conclusions:
- Sema4D acts as an intrinsic inhibitory regulator of oligodendrocyte differentiation.
- Sema4D promotes oligodendrocyte differentiation by inducing apoptosis.
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