Transgenic Research Center, School of Life Sciences, Northeast Normal University, Changchun, China.
Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, China.
PLoS One. 2019 Jul 10;14(7):e0213702. doi: 10.1371/journal.pone.0213702. eCollection 2019.
Disconnected interacting protein 2 homolog A (DIP2A) is highly expressed in nervous system and respiratory system of developing embryos. However, genes regulated by Dip2a in developing brain and lung have not been systematically studied. Transcriptome of brain and lung in embryonic 19.5 day (E19.5) were compared between wild type and Dip2a-/- mice. An average of 50 million reads per sample was mapped to the reference sequence. A total of 214 DEGs were detected in brain (82 up and 132 down) and 1900 DEGs in lung (1259 up and 641 down). GO enrichment analysis indicated that DEGs in both Brain and Lung were mainly enriched in biological processes 'DNA-templated transcription and Transcription from RNA polymerase II promoter', 'multicellular organism development', 'cell differentiation' and 'apoptotic process'. In addition, COG classification showed that both were mostly involved in 'Replication, Recombination, and Repair', 'Signal transduction and mechanism', 'Translation, Ribosomal structure and Biogenesis' and 'Transcription'. KEGG enrichment analysis showed that brain was mainly enriched in 'Thyroid cancer' pathway whereas lung in 'Complement and Coagulation Cascades' pathway. Transcription factor (TF) annotation analysis identified Zinc finger domain containing (ZF) proteins were mostly regulated in lung and brain. Interestingly, study identified genes Skor2, Gpr3711, Runx1, Erbb3, Frmd7, Fut10, Sox11, Hapln1, Tfap2c and Plxnb3 from brain that play important roles in neuronal cell maturation, differentiation, and survival; genes Hoxa5, Eya1, Errfi1, Sox11, Shh, Igf1, Ccbe1, Crh, Fgf9, Lama5, Pdgfra, Ptn, Rbp4 and Wnt7a from lung are important in lung development. Expression levels of the candidate genes were validated by qRT-PCR. Genome wide transcriptional analysis using wild type and Dip2a knockout mice in brain and lung at embryonic day 19.5 (E19.5) provided a genetic basis of molecular function of these genes.
连接蛋白相互作用蛋白 2 同源物 A（DIP2A）在发育中胚胎的神经系统和呼吸系统中高度表达。然而，在发育中的大脑和肺中受 Dip2a 调节的基因尚未被系统研究。在野生型和 Dip2a-/-小鼠中比较了胚胎 19.5 天（E19.5）的大脑和肺转录组。每个样本平均有 5000 万个读数映射到参考序列。在大脑中检测到 214 个差异表达基因（82 个上调和 132 个下调），在肺中检测到 1900 个差异表达基因（1259 个上调和 641 个下调）。GO 富集分析表明，大脑和肺中的差异表达基因主要富集于“DNA 模板转录和 RNA 聚合酶 II 启动子转录”、“多细胞生物发育”、“细胞分化”和“凋亡过程”等生物学过程。此外，COG 分类表明，两者主要涉及“复制、重组和修复”、“信号转导和机制”、“翻译、核糖体结构和生物发生”和“转录”。KEGG 富集分析表明，大脑主要富集于“甲状腺癌”途径，而肺主要富集于“补体和凝血级联”途径。转录因子（TF）注释分析确定锌指结构域蛋白（ZF）主要在肺和脑中受到调控。有趣的是，研究发现了 Skor2、Gpr3711、Runx1、Erbb3、Frmd7、Fut10、Sox11、Hapln1、Tfap2c 和 Plxnb3 等在神经元细胞成熟、分化和存活中发挥重要作用的基因；Hoxa5、Eya1、Errfi1、Sox11、Shh、Igf1、Ccbe1、Crh、Fgf9、Lama5、Pdgfra、Ptn、Rbp4 和 Wnt7a 等在肺发育中发挥重要作用的基因。通过 qRT-PCR 验证了候选基因的表达水平。使用野生型和 Dip2a 基因敲除小鼠在胚胎 19.5 天（E19.5）进行全基因组转录分析，为这些基因的分子功能提供了遗传基础。
