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The accessible chromatin landscape of the murine hippocampus at single-cell resolution.
Genome research Pub Date : 2019-04-01 , DOI: 10.1101/gr.243725.118
John R Sinnamon 1 , Kristof A Torkenczy 2 , Michael W Linhoff 1 , Sarah A Vitak 2 , Ryan M Mulqueen 2 , Hannah A Pliner 3 , Cole Trapnell 3 , Frank J Steemers 4 , Gail Mandel 1 , Andrew C Adey 2, 5, 6, 7
Affiliation  

Here we present a comprehensive map of the accessible chromatin landscape of the mouse hippocampus at single-cell resolution. Substantial advances of this work include the optimization of a single-cell combinatorial indexing assay for transposase accessible chromatin (sci-ATAC-seq); a software suite, scitools, for the rapid processing and visualization of single-cell combinatorial indexing data sets; and a valuable resource of hippocampal regulatory networks at single-cell resolution. We used sci-ATAC-seq to produce 2346 high-quality single-cell chromatin accessibility maps with a mean unique read count per cell of 29,201 from both fresh and frozen hippocampi, observing little difference in accessibility patterns between the preparations. By using this data set, we identified eight distinct major clusters of cells representing both neuronal and nonneuronal cell types and characterized the driving regulatory factors and differentially accessible loci that define each cluster. Within pyramidal neurons, we identified four major clusters, including CA1 and CA3 neurons, and three additional subclusters. We then applied a recently described coaccessibility framework, Cicero, which identified 146,818 links between promoters and putative distal regulatory DNA. Identified coaccessibility networks showed cell-type specificity, shedding light on key dynamic loci that reconfigure to specify hippocampal cell lineages. Lastly, we performed an additional sci-ATAC-seq preparation from cultured hippocampal neurons (899 high-quality cells, 43,532 mean unique reads) that revealed substantial alterations in their epigenetic landscape compared with nuclei from hippocampal tissue. This data set and accompanying analysis tools provide a new resource that can guide subsequent studies of the hippocampus.

中文翻译:

单细胞分辨率下的小鼠海马体染色质景观。

在这里,我们以单细胞分辨率展示了小鼠海马体可接近染色质景观的综合图谱。这项工作的实质性进展包括优化转座酶可及染色质的单细胞组合索引测定(sci-ATAC-seq);scitools 软件套件,用于快速处理和可视化单细胞组合索引数据集;以及单细胞分辨率的海马调节网络的宝贵资源。我们使用 sci-ATAC-seq 从新鲜和冷冻海马中生成 2346 个高质量单细胞染色质可及性图,每个细胞的平均独特读取计数为 29,201,观察到制备物之间的可及性模式几乎没有差异。通过使用该数据集,我们确定了代表神经元和非神经元细胞类型的八个不同的主要细胞簇,并表征了驱动调节因子和定义每个簇的差异可访问位点。在锥体神经元内,我们确定了四个主要簇,包括 CA1 和 CA3 神经元,以及三个附加子簇。然后,我们应用了最近描述的共可访问框架 Cicero,该框架识别了启动子和假定的远端调控 DNA 之间的 146,818 个链接。确定的共通网络显示出细胞类型特异性,揭示了重新配置以指定海马细胞谱系的关键动态位点。最后,我们对培养的海马神经元(899 个高质量细胞,43,532 个平均独特读数)进行了额外的 sci-ATAC-seq 准备,结果显示与海马组织的细胞核相比,其表观遗传景观发生了实质性变化。该数据集和随附的分析工具提供了可以指导后续海马体研究的新资源。
更新日期:2019-11-01
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