Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York, USA.
Center for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark.
Glia. 2023 Mar;71(3):524-540. doi: 10.1002/glia.24291. Epub 2022 Nov 5.
Genomic analyses have revealed heterogeneity among glial progenitor cells (GPCs), but the compartment selectivity of human GPCs (hGPCs) is unclear. Here, we asked if GPCs of human grey and white brain matter are distinct in their architecture and associated gene expression. RNA profiling of NG2-defined hGPCs derived from adult human neocortex and white matter differed in their expression of genes involved in Wnt, NOTCH, BMP and TGFβ signaling, suggesting compartment-selective biases in fate and self-renewal. White matter hGPCs over-expressed the BMP antagonists BAMBI and CHRDL1, suggesting their tonic suppression of astrocytic fate relative to cortical hGPCs, whose relative enrichment of cytoskeletal genes presaged their greater morphological complexity. In human glial chimeric mice, cortical hGPCs assumed larger and more complex morphologies than white matter hGPCs, and both were more complex than their mouse counterparts. These findings suggest that human grey and white matter GPCs comprise context-specific pools with distinct functional biases.
基因组分析揭示了神经胶质前体细胞（GPCs）之间的异质性，但人类 GPCs（hGPCs）的隔室选择性尚不清楚。在这里，我们想知道灰质和白质中的 GPC 是否在其结构和相关基因表达上存在差异。来自成人新皮质和白质的 NG2 定义的 hGPC 的 RNA 谱分析显示，其在 Wnt、NOTCH、BMP 和 TGFβ 信号通路相关基因的表达存在差异，表明命运和自我更新存在隔室选择性偏向。白质 hGPC 过度表达 BMP 拮抗剂 BAMBI 和 CHRDL1，表明它们对星形胶质细胞命运的持续抑制，而皮质 hGPC 中细胞骨架基因的相对富集预示着它们具有更大的形态复杂性。在人类胶质嵌合小鼠中，皮质 hGPC 比白质 hGPC 具有更大和更复杂的形态，并且都比其小鼠对应物更复杂。这些发现表明，人类灰质和白质 GPC 组成了具有独特功能偏向的特定于上下文的池。
