Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, 171 65, Solna, Sweden.
Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, 17177, Stockholm, Sweden.
BMC Biol. 2022 May 25;20(1):122. doi: 10.1186/s12915-022-01325-z.
Oligodendrocytes are glial cells that support and insulate axons in the central nervous system through the production of myelin. Oligodendrocytes arise throughout embryonic and early postnatal development from oligodendrocyte precursor cells (OPCs), and recent work demonstrated that they are a transcriptional heterogeneous cell population, but the regional and functional implications of this heterogeneity are less clear. Here, we apply in situ sequencing (ISS) to simultaneously probe the expression of 124 marker genes of distinct oligodendrocyte populations, providing comprehensive maps of the corpus callosum, cingulate, motor, and somatosensory cortex in the brain, as well as gray matter (GM) and white matter (WM) regions in the spinal cord, at postnatal (P10), juvenile (P20), and young adult (P60) stages. We systematically compare the abundances of these populations and investigate the neighboring preference of distinct oligodendrocyte populations.
We observed that oligodendrocyte lineage progression is more advanced in the juvenile spinal cord compared to the brain, corroborating with previous studies. We found myelination still ongoing in the adult corpus callosum while it was more advanced in the cortex. Interestingly, we also observed a lateral-to-medial gradient of oligodendrocyte lineage progression in the juvenile cortex, which could be linked to arealization, as well as a deep-to-superficial gradient with mature oligodendrocytes preferentially accumulating in the deeper layers of the cortex. The ISS experiments also exposed differences in abundances and population dynamics over time between GM and WM regions in the brain and spinal cord, indicating regional differences within GM and WM, and we found that neighboring preferences of some oligodendroglia populations are altered from the juvenile to the adult CNS.
Overall, our ISS experiments reveal spatial heterogeneity of oligodendrocyte lineage progression in the brain and spinal cord and uncover differences in the timing of oligodendrocyte differentiation and myelination, which could be relevant to further investigate functional heterogeneity of oligodendroglia, especially in the context of injury or disease.
少突胶质细胞是中枢神经系统中支持和隔离轴突的神经胶质细胞，通过髓鞘的产生来实现。少突胶质细胞在胚胎和出生后早期发育过程中由少突胶质前体细胞（OPC）产生，最近的研究表明它们是一个转录异质性的细胞群体，但这种异质性的区域和功能意义尚不清楚。在这里，我们应用原位测序（ISS）技术同时探测 124 种不同少突胶质细胞群体的标记基因的表达，为大脑胼胝体、扣带回、运动和体感皮层，以及脊髓灰质（GM）和白质（WM）区域提供了全面的图谱，在出生后（P10）、幼年期（P20）和青年期（P60）。我们系统地比较了这些群体的丰度，并研究了不同少突胶质细胞群体的邻近偏好。
我们观察到，与大脑相比，幼年脊髓中的少突胶质细胞谱系进展更为先进，这与之前的研究结果一致。我们发现，成年胼胝体中的髓鞘仍在进行，而皮层中的髓鞘则更为先进。有趣的是，我们还观察到，在幼年皮层中，少突胶质细胞谱系的进展存在从外侧到内侧的梯度，这可能与区域化有关，以及从深层到浅层的梯度，成熟的少突胶质细胞优先积累在皮层的深层。ISS 实验还揭示了大脑和脊髓中的 GM 和 WM 区域之间随时间推移的丰度和群体动态的差异，表明 GM 和 WM 内部存在区域差异，我们发现，一些少突胶质细胞群体的邻近偏好从幼年到成年中枢神经系统发生了改变。
总的来说，我们的 ISS 实验揭示了大脑和脊髓中少突胶质细胞谱系进展的空间异质性，并揭示了少突胶质细胞分化和髓鞘形成的时间差异，这可能与进一步研究少突胶质细胞的功能异质性有关，特别是在损伤或疾病的背景下。
