Glial progenitor cells of the adult human white and grey matter are contextually distinct.
Glial progenitor cells of the adult human white and grey matter are contextually distinct.
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基因组分析揭示了胶质祖细胞（GPC）之间的异质性，但人类GPC（hGPC）的隔室选择性尚不清楚。在这里，我们询问人类灰色和白色脑物质的GPCs在其结构和相关基因表达方面是否不同。来自成年人新皮质和白色物质的NG2定义的hGPCs的RNA分析在参与Wnt、NOTCH、BMP和TGFβ信号传导的基因表达方面存在差异，表明命运和自我更新的隔室选择性偏倚。白色hGPCs过度表达BMP拮抗剂BAMBI和CHRDL1，表明它们相对于皮质hGPCs对星形胶质细胞命运的紧张性抑制，皮质hGPCs细胞骨架基因的相对富集预示着它们更大的形态复杂性。在人类神经胶质嵌合体小鼠中，皮质hGPCs比白色物质hGPCs呈现更大和更复杂的形态，并且两者都比它们的小鼠对应物更复杂。这些发现表明，人类灰质和白色物质GPC包括具有不同功能偏倚的背景特异性池。成人白色和灰质中的GPCs在转录上是不同的。GM和WM hGPCs差异表达WNT、NOTCH、BMP和TGFβ通路基因。BMP拮抗剂在WM hGPCs中的表达显著更高。GM中的hGPCs比WM中的更大且更复杂。
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. GPCs in the adult human white and gray matter are transcriptionally distinct. GM and WM hGPCs differentially express WNT, NOTCH, BMP and TGFβ pathway genes. The expression of BMP antagonists is significantly higher in WM hGPCs. hGPCs in the GM are larger and more complex than in the WM.