Coordinated transcriptional shifts in microglia and oligodendrocytes from neurodevelopment to inflammaging

Glial cells shape brain development and aging, yet whether distinct glial lineages undergo coordinated lifespan transitions remains unclear. Although microglial aging states and oligodendrocyte vulnerability in neurodegeneration are well described, it remains unclear whether these programs evolve independently or in a temporally related manner. Here, we analyzed Mouse Cell Atlas single-cell RNA-seq data spanning embryogenesis to 24 months. Microglia and oligodendrocytes were the most transcriptionally dynamic glial populations, whereas astrocyte module activity was primarily observed during development. Microglia and oligodendrocytes exhibited similar late-life increases in inflammatory and senescence-associated modules, supported by cross-correlation (Pearson r ≈ 0.98; Max_CCF ≈ 0.98), dynamic time warping (DTW ≈ 6.16), and a large effect size (Cohen's d ≈ 11.08). These patterns were also supported by mixed glial contexts (p = 1.85 × 10⁻³). Together, these results identify a parallel transcriptional shift in microglia and oligodendrocytes from neurodevelopment to inflammaging and suggest that shared temporal programs across glial lineages may contribute to neurodegenerative vulnerability. This quantitative framework for assessing temporal similarity may be broadly applicable to other biological systems involving dynamic cellular state transitions.