Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, 17177, Stockholm, Sweden.
Biocant, Technology Transfer Association, Cantanhede, Portugal.
Nat Commun. 2020 Nov 17;11(1):5860. doi: 10.1038/s41467-020-19453-x.
Mature oligodendrocytes (MOLs) show transcriptional heterogeneity, the functional consequences of which are unclear. MOL heterogeneity might correlate with the local environment or their interactions with different neuron types. Here, we show that distinct MOL populations have spatial preference in the mammalian central nervous system (CNS). We found that MOL type 2 (MOL2) is enriched in the spinal cord when compared to the brain, while MOL types 5 and 6 (MOL5/6) increase their contribution to the OL lineage with age in all analyzed regions. MOL2 and MOL5/6 also have distinct spatial preference in the spinal cord regions where motor and sensory tracts run. OL progenitor cells (OPCs) are not specified into distinct MOL populations during development, excluding a major contribution of OPC intrinsic mechanisms determining MOL heterogeneity. In disease, MOL2 and MOL5/6 present different susceptibility during the chronic phase following traumatic spinal cord injury. Our results demonstrate that the distinct MOL populations have different spatial preference and different responses to disease.
成熟少突胶质细胞（MOL）表现出转录异质性，但其功能后果尚不清楚。MOL 异质性可能与局部环境或其与不同神经元类型的相互作用有关。在这里，我们表明不同的 MOL 群体在哺乳动物中枢神经系统（CNS）中具有空间偏好。我们发现，与大脑相比，MOL 类型 2（MOL2）在脊髓中更为丰富，而 MOL 类型 5 和 6（MOL5/6）在所有分析区域中随年龄增长增加了对 OL 谱系的贡献。MOL2 和 MOL5/6 在运动和感觉束运行的脊髓区域也具有不同的空间偏好。在发育过程中，少突胶质前体细胞（OPC）不会被特化为不同的 MOL 群体，这排除了 OPC 内在机制决定 MOL 异质性的主要作用。在疾病中，外伤性脊髓损伤后的慢性期 MOL2 和 MOL5/6 表现出不同的易感性。我们的结果表明，不同的 MOL 群体具有不同的空间偏好和对疾病的不同反应。
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