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Updated: Oct 9, 2025
Generation of Human Neurons and Oligodendrocytes from Pluripotent Stem Cells for Modeling Neuron-Oligodendrocyte Interactions
Published on: November 9, 2020
Microglia Impede Oligodendrocyte Generation in Aged Brain
Weimin Luan1,2, Xiqian Qi3, Feng Liang2
1Department of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
Purpose:
Age-related increase in myelin loss may be responsible for brain atrophy, and the mechanism is not completely understood. We aim to comprehensively delineate oligodendrocyte heterogeneity in young and aged mice and to reveal the underlying mechanism for myelin loss during aging.
Methods:
Diffusion tensor imaging and immunofluorescent staining were performed to verify the demyelination in the aged brains of both rodents and human. Further, the single-cell RNA sequencing data of all brain cells from young and aged mice were deeply analyzed to identify the subsets of oligodendrocyte lineage cells. Cell-to-cell interaction analysis was performed to detect the mechanism of observed changes in oligodendrocyte generation.
Results:
Oligodendrocytes were observed to up-regulate several senescence associated genes in aged brain. Four clusters of oligodendrocyte precursor cells (OPCs) were identified in both young and aged brains. The number of those OPCs in basal state was significantly increased, while the OPCs in the procedure of differentiation were immensely decreased in aged brain. Furthermore, it was identified that activated microglia in the aged brain released inflammatory factors to suppress OPC differentiation. Stat1 might be a potential target to transform senescent microglia into tissue repair type to promote oligodendrocyte generation.
Conclusion:
These results provided a perspective on how age activated microglia could impede remyelination and might give a new therapeutic target for age-related remyelinating diseases.
Insights
Aging brains show reduced myelin repair due to inflammatory microglia hindering oligodendrocyte precursor cell differentiation. Targeting Stat1 may restore tissue repair for remyelinating diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Aging Research
Background:
- Myelin loss contributes to age-related brain atrophy.
- The precise mechanisms driving age-related myelin loss remain unclear.
Purpose of the Study:
- To investigate oligodendrocyte heterogeneity in young versus aged mice.
- To elucidate the mechanisms behind myelin loss during brain aging.
Main Methods:
- Diffusion tensor imaging and immunofluorescent staining in rodents and humans.
- Single-cell RNA sequencing of mouse brain cells.
- Cell-to-cell interaction analysis to study oligodendrocyte generation.
Main Results:
- Aged oligodendrocytes exhibit increased senescence-associated genes.
- Four oligodendrocyte precursor cell (OPC) clusters were identified.
- Aged brains showed increased basal OPCs but decreased differentiating OPCs.
- Activated microglia release inflammatory factors inhibiting OPC differentiation.
- Stat1 identified as a potential target to promote oligodendrocyte generation.
Conclusions:
- Age-activated microglia impede remyelination by suppressing OPC differentiation.
- Targeting Stat1 may offer a therapeutic strategy for age-related remyelinating diseases.
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