Transcriptional Dynamics of Hair-Bundle Morphogenesis Revealed with CellTrails.
Transcriptional Dynamics of Hair-Bundle Morphogenesis Revealed with CellTrails.
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DOI：
10.1016/j.celrep.2018.05.002
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发表时间：
2018-06-05
期刊：
影响因子：
8.8
通讯作者：
Heller S
中科院分区：
文献类型：
--
作者：
Ellwanger DC;Scheibinger M;Dumont RA;Barr-Gillespie PG;Heller S
毛束从内耳感觉细胞的顶面伸出，进行机械转导。束生长涉及连续和重叠的细胞过程，这些过程隐藏在单个细胞的基因表达谱中。为了剖析这些过程，我们开发了CellTrails，这是一个用于发现、分析和可视化单细胞基因表达动力学的工具。利用发育中的鸡卵圆囊单个细胞的关键束蛋白的定量基因表达数据，我们重新构建了从祖细胞到成熟的纹状体和纹状体外毛细胞的分叉轨迹。发育轨迹的提取和比对以及假时间与束长度测量的关联将单个基因的表达动态与束生长阶段联系在一起。差异TRAIL分析揭示了控制纹状体和纹状体外束发育的转录本的高分辨率动力学，包括那些编码调节[Ca~(2+)]i或介导肌动蛋白细丝的交联和延长的蛋白质。使用转录切割数据沿着分支轨迹对单个细胞进行排序在生物信息学上是具有挑战性的。Ellwanger等人。开发了CellTrails，并应用该工具展示了随着感觉毛细胞发育成不同亚型的基因表达的分叉序列，这些亚型具有机械敏感型毛束的不同形态。
Protruding from the apical surface of inner ear sensory cells, hair bundles carry out mechanotransduction. Bundle growth involves sequential and overlapping cellular processes, which are concealed within gene expression profiles of individual cells. To dissect such processes, we developed CellTrails, a tool for uncovering, analyzing, and visualizing single-cell gene-expression dynamics. Utilizing quantitative gene-expression data for key bundle proteins from single cells of the developing chick utricle, we reconstructed de novo a bifurcating trajectory that spanned from progenitor cells to mature striolar and extrastriolar hair cells. Extraction and alignment of developmental trails and association of pseudo-time with bundle length measurements linked expression dynamics of individual genes with bundle growth stages. Differential trail analysis revealed high-resolution dynamics of transcripts that control striolar and extrastriolar bundle development, including those that encode proteins that regulate [Ca2+]i or mediate crosslinking and lengthening of actin filaments. Ordering single cells along branching trajectories using transcriptomic data is bioinformatically challenging. Ellwanger et al. developed CellTrails and applied this tool to showcase the bifurcating sequence of gene expression as sensory hair cells develop into different subtypes that feature spatially distinct morphologies of the mechanosensitive hair bundle.
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影响因子：
16.6
作者：
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通讯作者：
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影响因子：
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