Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate.
Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate.
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DOI：
10.7554/elife.31515
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发表时间：
2018-02-05
期刊：
影响因子：
7.7
通讯作者：
Bakkers J
中科院分区：
文献类型：
--
作者：
Burkhard SB;Bakkers J
心脏中特殊细胞和结构的发育受到空间限制的分子途径的调节。这些途径的破坏可能导致严重的先天性心脏畸形或功能缺陷。为了更好地了解这些途径以及它们如何调节心脏发育，我们使用 tomo-seq，将高通量 RNA 测序与组织切片相结合，为发育中的斑马鱼心脏建立具有高空间分辨率的全基因组表达数据集。对数据集的分析显示超过 1100 个基因在子区室中差异表达。窦房区的起搏细胞诱导心脏收缩，但对其发育的机制知之甚少。利用我们的转录组图谱，我们确定了起搏细胞中空间受限的 Wnt/β-catenin 信号传导活性，该活性由 Islet-1 活性控制。此外，Wnt/β-连环蛋白信号通过调节起搏器细胞对副交感神经刺激的反应来控制心率。因此，这种包含胚胎心脏中所有细胞类型的高分辨率转录组图谱可以揭示对特定心脏功能至关重要的空间受限分子途径。
Development of specialized cells and structures in the heart is regulated by spatially -restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, combining high-throughput RNA-sequencing with tissue-sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development. Using our transcriptome map, we identified spatially restricted Wnt/β-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/β-catenin signaling controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially restricted molecular pathways critical for specific cardiac functions.