Gene-expression analysis of hair cell regeneration in the zebrafish lateral line
Gene-expression analysis of hair cell regeneration in the zebrafish lateral line
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DOI：
10.1073/pnas.1402898111
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发表时间：
2014-04-08
影响因子：
11.1
通讯作者：
Piotrowski, Tatjana
中科院分区：
文献类型：
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作者：
Jiang, Linjia;Romero-Carvajal, Andres;Piotrowski, Tatjana
耳聋是由内耳毛细胞的最终丧失引起的，是最常见的感觉疾病之一。然而，非哺乳动物（如鸟类、两栖动物和鱼类）可以再生受损的毛细胞。为了更好地理解脊椎动物再生差异背后的原因，我们开始以高分辨率定义与斑马鱼侧线毛细胞再生相关的基因表达变化。我们对FACS纯化的再生支持细胞进行了RNA-Seq分析。得到的表达数据进行了途径富集分析，并通过全载原位杂交在体内验证了差异表达基因。我们发现，在毛细胞死亡后，细胞周期调节因子在Wnt/ β -连环蛋白信号激活前数小时表达。我们提出Wnt/ β -连环蛋白信号不参与调节增殖的开始，但在再生后期控制增殖。此外，与哺乳动物相比，我们的数据清楚地表明，Notch通路在损伤后不久显著下调，从而揭示了斑马鱼和哺乳动物对毛细胞损伤的反应之间的关键差异。综上所述，我们的发现为识别信号通路调节的差异奠定了基础，这些差异可以作为促进哺乳动物感觉上皮或毛细胞再生的潜在治疗靶点。
Deafness caused by the terminal loss of inner ear hair cells is one of the most common sensory diseases. However, nonmammalian animals (e. g., birds, amphibians, and fish) regenerate damaged hair cells. To understand better the reasons underpinning such disparities in regeneration among vertebrates, we set out to define at high resolution the changes in gene expression associated with the regeneration of hair cells in the zebrafish lateral line. We performed RNA-Seq analyses on regenerating support cells purified by FACS. The resulting expression data were subjected to pathway enrichment analyses, and the differentially expressed genes were validated in vivo via whole-mount in situ hybridizations. We discovered that cell cycle regulators are expressed hours before the activation of Wnt/beta-catenin signaling following hair cell death. We propose that Wnt/beta-catenin signaling is not involved in regulating the onset of proliferation but governs proliferation at later stages of regeneration. In addition, and in marked contrast to mammals, our data clearly indicate that the Notch pathway is significantly down-regulated shortly after injury, thus uncovering a key difference between the zebrafish and mammalian responses to hair cell injury. Taken together, our findings lay the foundation for identifying differences in signaling pathway regulation that could be exploited as potential therapeutic targets to promote either sensory epithelium or hair cell regeneration in mammals.