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Pathways that limit differentiation of oligodendrocyte progenitors in the aging brain

This study generated a transgenic mouse line that enables the in vivo visualization, isolation and transcriptional profiling of oligodendrocyte precursor cells (OPCs) across the lifespan. Analysis of gene-expression changes reveals how OPCs in the cerebral cortex respond to the aging brain environment and highlights pathways that inhibit their differentiation.

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Fig. 1: Generation of a large, comprehensive OPC transcriptomic dataset using Matn4-mEGFP reporter mouse line.

References

Bergles, D. E. & Richardson, W. D. Oligodendrocyte development and plasticity. Cold Spring Harb. Perspect. Biol. 8, a020453 (2015). This review discusses key features of OPCs during early development and in adult CNS.

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Neumann, B. et al. Myc determines the functional age state of oligodendrocyte progenitor cells. Nat. Aging 1, 826–837 (2021). This paper reports aging-associated changes in OPCs and demonstrates a genetic approach to restore the differentiation capacity of aged OPCs in vitro.

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Hughes, E. G., Kang, S. H., Fukaya, M. & Bergles, D. E. Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain. Nat. Neurosci. 16, 668–676 (2013). This paper defines the in vivo dynamics of mouse cortical OPCs in the adult brain.

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Buchanan, J., da Costa, N. M. & Cheadle, L. Emerging roles of oligodendrocyte precursor cells in neural circuit development and remodeling. Trends Neurosci. 46, 628–639 (2023). This review discusses nonprogenitor roles of OPCs in neuronal circuit remodeling and tissue repair.

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Spitzer, S. O. et al. Oligodendrocyte progenitor cells become regionally diverse and heterogeneous with age. Neuron 101, 459–471 (2019). This paper provides transcriptional and electrophysiological evidence for regional heterogeneity in OPCs across aging.

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This is a summary of: Heo, D. et al. Transcriptional profiles of mouse oligodendrocyte precursor cells across the lifespan. Nat. Aging https://doi.org/10.1038/s43587-025-00840-2 (2025).

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Pathways that limit differentiation of oligodendrocyte progenitors in the aging brain. Nat Aging (2025). https://doi.org/10.1038/s43587-025-00848-8

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Published:01 April 2025

DOI:https://doi.org/10.1038/s43587-025-00848-8

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