Large scale gene expression profiles of regenerating inner ear sensory epithelia.
Large scale gene expression profiles of regenerating inner ear sensory epithelia.
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DOI：
10.1371/journal.pone.0000525
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发表时间：
2007-06-13
期刊：
影响因子：
3.7
通讯作者：
Lovett M
中科院分区：
文献类型：
--
作者：
Hawkins RD;Bashiardes S;Powder KE;Sajan SA;Bhonagiri V;Alvarado DM;Speck J;Warchol ME;Lovett M
内耳感觉毛细胞（HC）的损失是人类听力损失和平衡障碍的主要原因。与哺乳动物不同，许多低等脊椎动物可以再生这些细胞。我们使用跨物种微阵列来检查鸟类内耳的这一过程。具体来说，研究了听觉和前庭器官毛细胞在两种不同损伤剂处理和体外再生后1700多个转录因子（TF）基因的表达变化。七个不同的已知信号通路的多个组分被清楚地识别出来：TGFβ、PAX、NOTCH、WNT、NFKappaB、胰岛素/IGF1和AP1。凋亡和细胞周期控制通路的许多组分差异表达，包括调节其表达的p27KIP和TFs。对不同组织和不同处理的表达趋势的比较揭示了在再生增殖过程中相同时间发生的相同表达模式。对这个大型数据集中基因表达模式的网络分析还揭示了雌激素受体信号、昼夜节律基因和部分多梳复合体（以及其他）的许多成分（和可能的网络相互作用）的额外存在。同样数量的差异表达基因被确定，但尚未被置于任何已知途径中。特定的时间点和组织也表现出有趣的差异：例如，45个锌指基因在耳蜗再生的后期被特异性上调。这些结果是同类研究中的第一个，应该为更详细地研究这些途径在HC恢复中的作用以及描述它们可能的相互作用提供起点。
Loss of inner ear sensory hair cells (HC) is a leading cause of human hearing loss and balance disorders. Unlike mammals, many lower vertebrates can regenerate these cells. We used cross-species microarrays to examine this process in the avian inner ear. Specifically, changes in expression of over 1700 transcription factor (TF) genes were investigated in hair cells of auditory and vestibular organs following treatment with two different damaging agents and regeneration in vitro. Multiple components of seven distinct known signaling pathways were clearly identifiable: TGFβ, PAX, NOTCH, WNT, NFKappaB, INSULIN/IGF1 and AP1. Numerous components of apoptotic and cell cycle control pathways were differentially expressed, including p27KIP and TFs that regulate its expression. A comparison of expression trends across tissues and treatments revealed identical patterns of expression that occurred at identical times during regenerative proliferation. Network analysis of the patterns of gene expression in this large dataset also revealed the additional presence of many components (and possible network interactions) of estrogen receptor signaling, circadian rhythm genes and parts of the polycomb complex (among others). Equal numbers of differentially expressed genes were identified that have not yet been placed into any known pathway. Specific time points and tissues also exhibited interesting differences: For example, 45 zinc finger genes were specifically up-regulated at later stages of cochlear regeneration. These results are the first of their kind and should provide the starting point for more detailed investigations of the role of these many pathways in HC recovery, and for a description of their possible interactions.
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