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Global Transcriptome Study of Dip2B-deficient Mouse Embryonic Lung Fibroblast Reveals its Important Roles in Cell Proliferation and Development
Computational and Structural Biotechnology Journal ( IF 6 ) Pub Date : 2020-09-05 , DOI: 10.1016/j.csbj.2020.08.030
Salah Adlat , Rajiv Kumar Sah , Farooq Hayel , Yang Chen , Fatoumata Binta Bah , Mahmoud Al-Azab , Noor Bahadar , May Myint , Zin Mar Oo , MI Nasser , Luqing Zhang , Xuechao Feng , Yaowu Zheng

Disco-interacting protein 2 homolog B (Dip2B) is a member of Dip2 family encoded by Dip2b gene. Dip2B has been reported to regulate murine epithelial KIT+ progenitor cell expansion and differentiation epigenetically via exosomal miRNA targeting during salivary gland organogenesis. However, its molecular functions, cellular activities and biological process remain unstudied. Here, we investigated the transcriptome of Dip2B-deficient mouse embryonic lung fibroblasts (MELFs) isolated from E14.5 embryos by RNA-Seq. Expression profiling identified 1369 and 1104 differentially expressed genes (DEGs) from Dip2b-/- and Dip2b+/- MELFs in comparisons to wild-type (Dip2b+/+). Functional clustering of DEGs revealed that many gene ontology terms belong to membrane activities such as ‘integral component of plasma membrane’, and ‘ion channel activity’, suggesting possible roles of Dip2B in membrane integrity and membrane function. KEGG pathway analysis revealed that multiple metabolic pathways are affected in Dip2b-/- and Dip2b+/- when compared to Dip2b+/+ MELFs. These include ‘protein digestion and absorption’, ‘pancreatic secretion’ and ‘steroid hormone synthesis pathway’. These results suggest that Dip2B may play important roles in metabolism. Molecular function analysis shows transcription factors including Hox-genes, bHLH-genes, and Forkhead-genes are significantly down-regulated in Dip2b-/- MELFs. These genes are critical in embryo development and cell differentiation. In addition, Dip2B-deficient MELFs demonstrated a reduction in cell proliferation and migration, and an increase in apoptosis. All results indicate that Dip2B plays multiple roles in cell proliferation, migration and apoptosis during embryogenesis and may participate in control of metabolism. This study provides valuable information for further understanding of the function and regulatory mechanisms of Dip2B.



中文翻译:

Dip2B缺陷小鼠胚胎肺成纤维细胞的全球转录组研究显示其在细胞增殖和发育中的重要作用。

迪斯科相互作用蛋白2同源物B(Dip2B)是Dip2b基因编码的Dip2家族的成员。据报道,Dip2B通过唾液腺器官发生过程中的外泌体miRNA靶向调控小鼠上皮KIT +祖细胞的表观遗传扩增和分化。然而,其分子功能,细胞活性和生物学过程仍未研究。在这里,我们研究了通过RNA-Seq从E14.5胚胎分离的Dip2B缺陷型小鼠胚胎肺成纤维细胞(MELFs)的转录组。表达谱鉴定与野生型(Dip2b + / +)相比,来自Dip2b -/-Dip2b +/- MELFs的1369和1104个差异表达基因(DEGs))。DEGs的功能聚类表明,许多基因本体术语都属于膜活动,例如“质膜的整体组成部分”和“离子通道活性”,这表明Dip2B在膜完整性和膜功能中可能发挥作用。KEGG途径分析显示,与Dip2b + / + MELF相比,Dip2b -/-Dip2b +/-中有多个代谢途径受到影响。这些包括“蛋白质消化吸收”,“胰腺分泌”和“类固醇激素合成途径”。这些结果表明,Dip2B可能在代谢中起重要作用。分子功能分析显示转录因子包括Hox-Dip2b -/- MELFs基因,bHLH基因和Forkhead基因被显着下调。这些基因在胚胎发育和细胞分化中至关重要。此外,Dip2B缺陷的MELF表现出细胞增殖和迁移的减少以及细胞凋亡的增加。所有结果表明,Dip2B在胚胎发生过程中在细胞增殖,迁移和凋亡中起多种作用,并可能参与代谢的控制。这项研究为进一步了解Dip2B的功能和调节机制提供了有价值的信息。

更新日期:2020-09-07
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