关键词: Pax8 astrocyte heterogeneity energy provisioning optic nerve head retinal astrocytes transcriptional profile white matter astrocytes

Mesh : Astrocytes / metabolism Animals Retina / metabolism cytology Mice, Inbred C57BL Gene Expression Profiling / methods Mice Optic Nerve / metabolism Transcriptome

来  源:   DOI:10.1002/glia.24571   PDF(Pubmed)

Abstract:
Astrocyte heterogeneity is an increasingly prominent research topic, and studies in the brain have demonstrated substantial variation in astrocyte form and function, both between and within regions. In contrast, retinal astrocytes are not well understood and remain incompletely characterized. Along with optic nerve astrocytes, they are responsible for supporting retinal ganglion cell axons and an improved understanding of their role is required. We have used a combination of microdissection and Ribotag immunoprecipitation to isolate ribosome-associated mRNA from retinal astrocytes and investigate their transcriptome, which we also compared to astrocyte populations in the optic nerve. Astrocytes from these regions are transcriptionally distinct, and we identified retina-specific astrocyte genes and pathways. Moreover, although they share much of the \"classical\" gene expression patterns of astrocytes, we uncovered unexpected variation, including in genes related to core astrocyte functions. We additionally identified the transcription factor Pax8 as a highly specific marker of retinal astrocytes and demonstrated that these astrocytes populate not only the retinal surface, but also the prelaminar region at the optic nerve head. These findings are likely to contribute to a revised understanding of the role of astrocytes in the retina.
摘要:
星形胶质细胞异质性是一个日益突出的研究课题,大脑中的研究表明,星形胶质细胞的形式和功能有很大的变化,在区域之间和区域内。相比之下,视网膜星形胶质细胞尚未得到很好的理解,并且仍未完全表征。连同视神经星形胶质细胞,它们负责支持视网膜神经节细胞轴突,需要更好地理解它们的作用。我们使用显微切割和Ribotag免疫沉淀的组合从视网膜星形胶质细胞中分离核糖体相关mRNA,并研究其转录组。我们还将其与视神经中的星形胶质细胞进行了比较。来自这些区域的星形胶质细胞在转录上是不同的,我们确定了视网膜特异性星形胶质细胞基因和通路。此外,尽管它们共享星形胶质细胞的“经典”基因表达模式,我们发现了意想不到的变化,包括与核心星形胶质细胞功能相关的基因。我们还将转录因子Pax8鉴定为视网膜星形胶质细胞的高度特异性标记,并证明这些星形胶质细胞不仅存在于视网膜表面,还有视神经乳头的前层区域。这些发现可能有助于对星形胶质细胞在视网膜中的作用进行修订的理解。
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