Brain-wide mapping of oligodendrocyte organization, oligodendrogenesis, and myelin injury
Summary
Insulating sheaths of myelin accelerate neuronal communication in the mammalian brain. Oligodendrocytes that produce myelin are generated throughout life to gradually increase myelin coverage, but these dynamics have not been defined brain-wide across the lifespan. We developed a cellular mapping pipeline involving tissue clearing, lightsheet microscopy, and AI-assisted analysis to identify the precise location of millions of oligodendrocytes and assess regional myelin density in the mouse
Content
# Brain-wide mapping of oligodendrocyte organization, oligodendrogenesis, and myelin injury
*Published: 2026 Mar 5*
Insulating sheaths of myelin accelerate neuronal communication in the mammalian
brain. Oligodendrocytes that produce myelin are generated throughout life to
gradually increase myelin coverage, but these dynamics have not been defined
brain-wide across the lifespan. We developed a cellular mapping pipeline
involving tissue clearing, lightsheet microscopy, and AI-assisted analysis to
identify the precise location of millions of oligodendrocytes and assess
regional myelin density in the mouse brain. These atlases revealed the diversity
of oligodendrocyte patterning, which was consistent between brain hemispheres,
individuals, and sexes but displayed both age- and region-specific differences.
Integration of these atlases with transcriptomic and ultrastructural datasets
highlighted underlying mechanisms that may control this patterning. In models of
demyelination and disease, we identified regions of enhanced oligodendrocyte
resilience and vulnerability and white matter injury near β-amyloid plaques,
demonstrating the utility of this pipeline for defining brain-wide
oligodendrocyte dynamics in both health and disease.
DOI: 10.1016/j.cell.2026.01.025