Genome-wide analysis reveals conserved transcriptional responses downstream of resting potential change in Xenopus embryos, axolotl regeneration, and human mesenchymal cell differentiation.
Genome-wide analysis reveals conserved transcriptional responses downstream of resting potential change in Xenopus embryos, axolotl regeneration, and human mesenchymal cell differentiation.
复制标题
全基因组分析揭示了爪蟾胚胎，阿克索氏菌再生和人间充质细胞分化的静止势变化下游的保守转录反应。
DOI：
10.1002/reg2.48
复制
发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Levin M
中科院分区：
文献类型：
--
作者：
Pai VP;Martyniuk CJ;Echeverri K;Sundelacruz S;Kaplan DL;Levin M
通过细胞静息电位（V_p）变化的内源性生物电信号传导是许多模型系统中再生和胚胎发生期间图案形成的关键调节剂。V β的去极化在功能上与去分化、肿瘤发生、解剖学重新指定和附件再生有关。然而，尚未进行无偏分析以了解体内全基因组对V β变化的转录反应。此外，还不知道哪些基因或基因网络代表了不同模式背景和物种中生物电信号的保守靶标。在这里，我们使用微阵列分析来比较分析转录响应V β去极化。我们比较了胚胎发生（非洲爪蟾发育），再生（蝾螈再生）和干细胞分化（培养中的人类间充质干细胞）过程中转录组的反应，以确定与去极化相关的跨模型物种的共同网络。子网络富集和PANTHER分析都确定了许多关键的遗传模块作为V_（10）变化的靶点，并且还揭示了生物电信号转导中重要的（保守的）共性，尽管实验背景和物种高度多样。去极化调节所有三个胚层（外胚层，中胚层和内胚层）的特定转录网络，如细胞分化和凋亡，这些信息将用于开发生物电调节模式的机制模型。此外，我们的分析表明，V β变化调节与重要疾病途径（如癌症和神经退行性疾病）相关的转录物，这可能是新兴的电疗法的新靶点。
Endogenous bioelectric signaling via changes in cellular resting potential (V mem) is a key regulator of patterning during regeneration and embryogenesis in numerous model systems. Depolarization of V mem has been functionally implicated in dedifferentiation, tumorigenesis, anatomical re‐specification, and appendage regeneration. However, no unbiased analyses have been performed to understand genome‐wide transcriptional responses to V mem change in vivo. Moreover, it is unknown which genes or gene networks represent conserved targets of bioelectrical signaling across different patterning contexts and species. Here, we use microarray analysis to comparatively analyze transcriptional responses to V mem depolarization. We compare the response of the transcriptome during embryogenesis (Xenopus development), regeneration (axolotl regeneration), and stem cell differentiation (human mesenchymal stem cells in culture) to identify common networks across model species that are associated with depolarization. Both subnetwork enrichment and PANTHER analyses identified a number of key genetic modules as targets of V mem change, and also revealed important (well‐conserved) commonalities in bioelectric signal transduction, despite highly diverse experimental contexts and species. Depolarization regulates specific transcriptional networks across all three germ layers (ectoderm, mesoderm, and endoderm) such as cell differentiation and apoptosis, and this information will be used for developing mechanistic models of bioelectric regulation of patterning. Moreover, our analysis reveals that V mem change regulates transcripts related to important disease pathways such as cancer and neurodegeneration, which may represent novel targets for emerging electroceutical therapies.