Comparative RNA-seq analysis in the unsequenced axolotl: the oncogene burst highlights early gene expression in the blastema.
Comparative RNA-seq analysis in the unsequenced axolotl: the oncogene burst highlights early gene expression in the blastema.
复制标题
DOI：
10.1371/journal.pcbi.1002936
复制
发表时间：
2013
影响因子：
4.3
通讯作者：
Dewey CN
中科院分区：
文献类型：
--
作者：
Stewart R;Rascón CA;Tian S;Nie J;Barry C;Chu LF;Ardalani H;Wagner RJ;Probasco MD;Bolin JM;Leng N;Sengupta S;Volkmer M;Habermann B;Tanaka EM;Thomson JA;Dewey CN
蝾螈具有截肢后肢体再生的非凡能力。截肢部位的细胞形成胚基，然后增殖和分化以重新长出肢体。为了更好地理解这一过程，我们在一段时间内对蝾螈（一种基因组尚未测序的物种）的芽基进行了深度 RNA 测序。使用一种新颖的比较方法来分析 RNA-seq 数据，我们描述了再生蝾螈肢体相对于人类基因集的转录动力学。该方法涉及从头组装蝾螈转录本、在没有参考基因组的情况下进行 RNA-seq 转录本定量，以及将丰度从蝾螈重叠群转化为人类基因。我们发现癌基因表达在第一天出现显着爆发，胚芽/肢芽基因在 7 至 14 天达到峰值。此外，我们发现肢体模式基因、SALL基因以及参与血管生成、伤口愈合、防御/免疫和骨发育的基因在芽基形成和发育过程中丰富。最后，我们确定了一类先前没有文献支持肢体再生的基因，根据它们在再生过程中的表达模式，这些基因是进一步评估的候选基因。像蝾螈这样的蝾螈在截肢后可以完全再生肢体，使它们成为脊椎动物的再生冠军。另一方面，人类和其他哺乳动物的肢体结构再生能力非常有限。了解蝾螈在肢体再生过程中激活的基因、基因网络和通路将为改善哺乳动物的再生反应提供线索。然而，阐明这些基因、网络和途径很困难，因为蝾螈的基因组尚未测序，而且它在进化上与基因组测序的物种有所不同。在这里，我们通过 RNA 测序 (RNA-seq) 为蝾螈生成了一组基因转录本，并提供了有关再生过程中激活的基因性质的信息。为了确定这些蝾螈基因的身份，我们使用比较转录组学技术将蝾螈转录数据与注释良好的人类基因集的数据进行匹配。支持之前的研究，我们发现许多先前发现与肢体发育和再生有关的基因上调。此外，我们在再生的第一阶段发现了大量与癌症相关的基因，并鉴定了一组以前与再生过程无关的基因。
The salamander has the remarkable ability to regenerate its limb after amputation. Cells at the site of amputation form a blastema and then proliferate and differentiate to regrow the limb. To better understand this process, we performed deep RNA sequencing of the blastema over a time course in the axolotl, a species whose genome has not been sequenced. Using a novel comparative approach to analyzing RNA-seq data, we characterized the transcriptional dynamics of the regenerating axolotl limb with respect to the human gene set. This approach involved de novo assembly of axolotl transcripts, RNA-seq transcript quantification without a reference genome, and transformation of abundances from axolotl contigs to human genes. We found a prominent burst in oncogene expression during the first day and blastemal/limb bud genes peaking at 7 to 14 days. In addition, we found that limb patterning genes, SALL genes, and genes involved in angiogenesis, wound healing, defense/immunity, and bone development are enriched during blastema formation and development. Finally, we identified a category of genes with no prior literature support for limb regeneration that are candidates for further evaluation based on their expression pattern during the regenerative process. Salamanders such as the axolotl can fully regenerate a limb upon amputation, making them the vertebrate champions of regeneration. On the other hand, humans and other mammals possess a very limited ability to regenerate limb structures. Learning about the genes, gene networks, and pathways activated in the salamander during limb regeneration will provide cues to improving the regenerative response in mammals. Elucidating these genes, networks, and pathways is difficult, however, because the axolotl does not yet have its genome sequenced and because it has diverged evolutionarily from species with a sequenced genome. Here, we produce a set of gene transcripts via RNA sequencing (RNA-seq) for the axolotl and provide information on the nature of the genes activated during regeneration. To determine the identity of these axolotl genes, we use comparative transcriptomics techniques to match the axolotl transcript data to that of the well-annotated human gene set. Supporting previous studies, we find upregulation of many genes previously found to be involved in limb development and regeneration. In addition, we find a burst of cancer-related genes during the first phase of regeneration and identify a set of genes previously not associated with the regeneration process.
登录
查看更多内容
影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
DOI：
10.1016/j.bbrc.2006.07.124
发表时间：
2006-09-29
影响因子：
3.1
作者：
Boehm, Johann;Sustmann, Claudio;Kohlhase, Juergen
通讯作者：
Kohlhase, Juergen
影响因子：
20.3
作者：
Aguila, Jerell R.;Liao, Wenbin;Ma, Yupo
通讯作者：
Ma, Yupo
影响因子：
11.2
作者：
Federico, Antonella;Pallante, Pierlorenzo;Fusco, Alfredo
通讯作者：
Fusco, Alfredo
影响因子：
4.5
作者：
Gaspar C;Franken P;Molenaar L;Breukel C;van der Valk M;Smits R;Fodde R
通讯作者：
Fodde R