Transcriptomic changes during regeneration of the central nervous system in an echinoderm.

Transcriptomic changes during regeneration of the central nervous system in an echinoderm.
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转录组中枢神经系统在棘皮动物中的再生过程中的变化。

DOI:
10.1186/1471-2164-15-357
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发表时间:
2014-05-12
期刊:
影响因子:
4.4
通讯作者:
García-Arrarás JE
García-Arrarás JE
中科院分区:
生物学2区
文献类型:
--
作者:
Mashanov VS;Zueva OR;García-Arrarás JE

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棘皮动物正在成为再生生物学的重要模型。关于这些动物创伤后修复的细胞机制的大量数据是可用的,而对基因表达的研究却很少。在这项研究中,我们采用高通量测序分析了海参Holothuria glaberrima中正常和再生的桡神经索(脊索神经管的同源物)的转录组。我们的重新组装得到70,173个contigs,其中24,324个显示出与已知蛋白质编码序列的显著相似性。表达谱显示了与再生相关的基因表达的大规模变化(分别为4,023和3,257个上调和下调的转录本)。对差异表达基因集的功能分析表明,最广泛被过度代表的途径是那些参与细胞外基质(ECM)重塑和ECM-细胞相互作用的途径,这表明ECM在再生中起关键作用。我们还搜索了海参转录组中已知参与多能性获得和/或控制的同源因子。我们发现了11个在正常组织和再生组织中都表达的基因。其中,只有Myc在再生中显著升高,而Bmi-1的表达显著降低。我们还试图深入了解哪些转录因子可能在调控层次的顶端运作,以控制再生中的基因表达。我们的分析产生了11个可能的转录因子,它们构成了进一步功能研究的良好候选者。确定的候选转录因子不仅包括已知的再生相关基因,还包括以前未涉及的创伤后组织再生调节因子。功能注释还表明,棘皮动物快速有效的神经再生可能与抑制兴奋性毒性有关。我们的转录组学分析证实了有关海参再生的细胞机制的现有数据。然而,更重要的是,它也阐明了棘皮动物再生的新方面,这些方面几乎没有被研究或完全忽视。本研究最重要的成果是,通过提供用于功能分析的关键候选基因列表,为未来的调控机制研究制定了路线图。
Echinoderms are emerging as important models in regenerative biology. Significant amount of data are available on cellular mechanisms of post-traumatic repair in these animals, whereas studies of gene expression are rare. In this study, we employ high-throughput sequencing to analyze the transcriptome of the normal and regenerating radial nerve cord (a homolog of the chordate neural tube), in the sea cucumber Holothuria glaberrima. Our de novo assembly yielded 70,173 contigs, of which 24,324 showed significant similarity to known protein-coding sequences. Expression profiling revealed large-scale changes in gene expression (4,023 and 3,257 up-regulated and down-regulated transcripts, respectively) associated with regeneration. Functional analysis of sets of differentially expressed genes suggested that among the most extensively over-represented pathways were those involved in the extracellular matrix (ECM) remodeling and ECM-cell interactions, indicating a key role of the ECM in regeneration. We also searched the sea cucumber transcriptome for homologs of factors known to be involved in acquisition and/or control of pluripotency. We identified eleven genes that were expressed both in the normal and regenerating tissues. Of these, only Myc was present at significantly higher levels in regeneration, whereas the expression of Bmi-1 was significantly reduced. We also sought to get insight into which transcription factors may operate at the top of the regulatory hierarchy to control gene expression in regeneration. Our analysis yielded eleven putative transcription factors, which constitute good candidates for further functional studies. The identified candidate transcription factors included not only known regeneration-related genes, but also factors not previously implicated as regulators of post-traumatic tissue regrowth. Functional annotation also suggested that one of the possible adaptations contributing to fast and efficient neural regeneration in echinoderms may be related to suppression of excitotoxicity. Our transcriptomic analysis corroborates existing data on cellular mechanisms implicated in regeneration in sea cucumbers. More importantly, however, it also illuminates new aspects of echinoderm regeneration, which have been scarcely studied or overlooked altogether. The most significant outcome of the present work is that it lays out a roadmap for future studies of regulatory mechanisms by providing a list of key candidate genes for functional analysis.
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