Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Nat Neurosci. 2024 May;27(5):846-861. doi: 10.1038/s41593-024-01613-7. Epub 2024 Mar 27.
The generation of new myelin-forming oligodendrocytes in the adult central nervous system is critical for cognitive function and regeneration following injury. Oligodendrogenesis varies between gray and white matter regions, suggesting that local cues drive regional differences in myelination and the capacity for regeneration. However, the layer- and region-specific regulation of oligodendrocyte populations is unclear due to the inability to monitor deep brain structures in vivo. Here we harnessed the superior imaging depth of three-photon microscopy to permit long-term, longitudinal in vivo three-photon imaging of the entire cortical column and subcortical white matter in adult mice. We find that cortical oligodendrocyte populations expand at a higher rate in the adult brain than those of the white matter. Following demyelination, oligodendrocyte replacement is enhanced in the white matter, while the deep cortical layers show deficits in regenerative oligodendrogenesis and the restoration of transcriptional heterogeneity. Together, our findings demonstrate that regional microenvironments regulate oligodendrocyte population dynamics and heterogeneity in the healthy and diseased brain.
成年中枢神经系统中新生髓鞘形成少突胶质细胞对于认知功能和损伤后再生至关重要。少突胶质细胞发生在灰质和白质区域之间，这表明局部线索驱动了髓鞘形成和再生能力的区域差异。然而，由于无法在体内监测深部脑结构，少突胶质细胞群体的分层和区域特异性调节尚不清楚。在这里，我们利用三光子显微镜的卓越成像深度，允许在成年小鼠体内进行整个皮质柱和皮质下白质的长期、纵向三光子成像。我们发现，与白质中的少突胶质细胞群体相比，成年大脑中的皮质少突胶质细胞群体以更高的速度扩张。脱髓鞘后，白质中的少突胶质细胞替代增强，而深层皮质层在再生性少突胶质发生和转录异质性的恢复方面表现出缺陷。总之，我们的研究结果表明，区域微环境调节健康和患病大脑中少突胶质细胞群体的动力学和异质性。
