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发育中的星形胶质细胞初级纤毛的基因标记

genetic labeling of primary cilia in developing astrocytes.

作者信息

Bear Rachel, Wei Claire, Caspary Tamara

机构信息

Department of Human Genetics, Emory University School of Medicine, 615 Michael Street Suite 301, Atlanta GA 30322, United States.

Emory Graduate Program in Neuroscience.

出版信息

bioRxiv. 2025 Mar 19:2025.03.19.644181. doi: 10.1101/2025.03.19.644181.

Abstract

Astrocyte cilia are largely understudied due to the lack of available tools. Astrocyte research advanced with the establishment of , an inducible Cre line that specifically targets the astrocyte lineage. Here, we develop and compare genetic models that label astrocyte cilia in the developing prefrontal cortex (PFC) using and Cre-dependent cilia reporters. We evaluate these models by testing different tamoxifen-induction protocols and quantifying the percentage of astrocytes labeled with the cilia reporters. We show that tamoxifen dosage impacts the expression of cilia reporters in astrocytes. We validate the maximum cilia-labeling efficiency of tamoxifen using constitutively-expressed cilia reporters. The data reveal that only a subset of SOX9- positive astrocytes in the PFC possess cilia throughout development. Our work highlights the utility of Cre-Lox systems to target specific cell types and the importance of carefully validating genetic models.

摘要

由于缺乏可用的工具,星形胶质细胞的纤毛在很大程度上未得到充分研究。随着 的建立,星形胶质细胞的研究取得了进展,这是一种可诱导的Cre系,专门针对星形胶质细胞谱系。在这里,我们开发并比较了使用 和Cre依赖性纤毛报告基因标记发育中的前额叶皮质(PFC)中星形胶质细胞纤毛的遗传模型。我们通过测试不同的他莫昔芬诱导方案并量化用纤毛报告基因标记的星形胶质细胞的百分比来评估这些模型。我们表明他莫昔芬剂量会影响星形胶质细胞中纤毛报告基因的表达。我们使用组成型表达的纤毛报告基因验证了他莫昔芬的最大纤毛标记效率。数据显示,在整个发育过程中,PFC中只有一部分SOX9阳性星形胶质细胞具有纤毛。我们的工作突出了Cre-Lox系统靶向特定细胞类型的效用以及仔细验证遗传模型的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/131c/11957109/429bc51d6ecb/nihpp-2025.03.19.644181v1-f0001.jpg

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