通过对小鼠小脑的 Bergmann 胶质细胞进行单细胞转录组分析鉴定新型神经胶质基因。

Identification of novel glial genes by single-cell transcriptional profiling of Bergmann glial cells from mouse cerebellum.

机构信息

F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Massachusetts, United States of America.

出版信息

PLoS One. 2010 Feb 12;5(2):e9198. doi: 10.1371/journal.pone.0009198.

Abstract

Bergmann glial cells play critical roles in the structure and function of the cerebellum. During development, their radial processes serve as guides for migrating granule neurons and their terminal endfeet tile to form the glia limitans. As the cerebellum matures, Bergmann glia perform important roles in synaptic transmission and synapse maintenance, while continuing to serve as essential structural elements. Despite growing evidence of the diverse functions of Bergmann glia, the molecular mechanisms that mediate these functions have remained largely unknown. As a step toward identifying the molecular repertoire underlying Bergmann glial function, here we examine global gene expression in individual Bergmann glia from developing (P6) and mature (P30) mouse cerebellum. When we select for developmentally regulated genes, we find that transcription factors and ribosomal genes are particularly enriched at P6 relative to P30; whereas synapse associated molecules are enriched at P30 relative to P6. We also analyze genes expressed at high levels at both ages. In all these categories, we find genes that were not previously known to be expressed in glial cells, and discuss novel functions some of these genes may potentially play in Bergmann glia. We also show that Bergmann glia, even in the adult, express a large set of genes thought to be specific to stem cells, suggesting that Bergmann glia may retain neural precursor potential as has been proposed. Finally, we highlight several genes that in the cerebellum are expressed in Bergmann glia but not astrocytes, and may therefore serve as new, specific markers for Bergmann glia.

摘要

Bergmann 胶质细胞在小脑的结构和功能中起着关键作用。在发育过程中,它们的放射状突起作为迁移颗粒神经元的引导,其末端足板形成胶质界膜。随着小脑的成熟,Bergmann 胶质细胞在突触传递和突触维持中发挥重要作用,同时继续作为重要的结构元件。尽管 Bergmann 胶质细胞的多种功能有越来越多的证据,但介导这些功能的分子机制在很大程度上仍然未知。为了确定 Bergmann 胶质细胞功能的分子组成,我们在此检查了来自发育(P6)和成熟(P30)小鼠小脑的单个 Bergmann 胶质细胞的全基因表达。当我们选择发育调节基因时,我们发现转录因子和核糖体基因在 P6 时相对 P30 更为丰富;而突触相关分子在 P30 时相对 P6 更为丰富。我们还分析了在两个年龄段都高表达的基因。在所有这些类别中,我们都发现了以前未知在神经胶质细胞中表达的基因,并讨论了其中一些基因在 Bergmann 胶质细胞中可能具有的新功能。我们还表明,即使在成年期,Bergmann 胶质细胞也表达了一大组被认为是干细胞特有的基因,这表明 Bergmann 胶质细胞可能像之前提出的那样保留了神经前体细胞的潜力。最后,我们强调了几个在小脑中仅在 Bergmann 胶质细胞中表达而不在星形胶质细胞中表达的基因,因此可能成为 Bergmann 胶质细胞的新的、特异性标记物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d2b/2820553/339cb1378259/pone.0009198.g001.jpg

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