A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors.
A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors.
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DOI：
10.1016/j.celrep.2016.12.063
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发表时间：
2017-01-17
期刊：
影响因子：
8.8
通讯作者：
Whited JL
中科院分区：
文献类型：
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作者：
Bryant DM;Johnson K;DiTommaso T;Tickle T;Couger MB;Payzin-Dogru D;Lee TJ;Leigh ND;Kuo TH;Davis FG;Bateman J;Bryant S;Guzikowski AR;Tsai SL;Coyne S;Ye WW;Freeman RM Jr;Peshkin L;Tabin CJ;Regev A;Haas BJ;Whited JL
哺乳动物的再生能力极其有限；然而，蝾螈具有很强的再生能力，可以替换整个四肢。肢体再生的机制仍然知之甚少，部分原因是由于蝾螈巨大且不完整的基因组测序阻碍了促进再生基因的研究。我们利用广泛组织的rna测序图谱组装并注释了一个全新的转录组，估计该转录组具有88%的美西螈基因的近乎完整的序列信息。我们设计了表达分析，确定了cirbp和kazald1的美西螈同源基因在胚芽中高度表达和富集。利用morpholino反义寡核苷酸，我们发现cirbp在肢体再生过程中发挥细胞保护作用，而操纵kazald1表达会破坏再生。我们的转录组和注释资源极大地补充了以前的转录组研究，将成为未来再生生物学研究的宝贵资源。
Mammals have extremely limited regenerative capabilities; however, axolotls are profoundly regenerative and can replace entire limbs. The mechanisms underlying limb regeneration remain poorly understood, partly because the enormous and incompletely sequenced genomes of axolotls have hindered the study of genes facilitating regeneration. We assembled and annotated a de novo transcriptome using RNA-sequencing profiles for a broad spectrum of tissues that is estimated to have near-complete sequence information for 88% of axolotl genes. We devised expression analyses that identified the axolotl orthologs of cirbp and kazald1 as highly expressed and enriched in blastemas. Using morpholino anti-sense oligonucleotides, we find evidence that cirbp plays a cytoprotective role during limb regeneration while manipulation of kazald1 expression disrupts regeneration. Our transcriptome and annotation resources greatly complement previous transcriptomic studies and will be a valuable resource for future research in regenerative biology.