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Identification of differentially expressed hematopoiesis-associated genes in term low birth weight newborns by systems genomics approach
Current Genomics ( IF 2.6 ) Pub Date : 2020-01-01 , DOI: 10.2174/1389202920666191203123025
Sakshi Singh 1 , Vinay K Singh 1 , Geeta Rai 1
Affiliation  

Background Low Birth Weight (LBW) (birth weight <2.5 Kg) newborns are associated with a high risk of infection, morbidity and mortality during their perinatal period. Compromised innate immune responses and inefficient hematopoietic differentiation in term LBW newborns led us to evaluate the gene expression status of hematopoiesis. Materials and Methods In this study, we compared our microarray datasets of LBW-Normal Birth Weight (NBW) newborns with two reference datasets to identify hematopoietic stem cells genes, and their differential expression in the LBW newborns, by hierarchical clustering algorithm using gplots and RcolorBrewer package in R. Results Comparative analysis revealed 108 differentially expressed hematopoiesis genes (DEHGs), of which 79 genes were up-regulated, and 29 genes were down-regulated in LBW newborns compared to their NBW counterparts. Moreover, protein-protein interactions, functional annotation and pathway analysis demonstrated that the up-regulated genes were mainly involved in cell proliferation and differentiation, MAPK signaling and Rho GTPases signaling, and the down-regulated genes were engaged in cell proliferation and regulation, immune system regulation, hematopoietic cell lineage and JAK-STAT pathway. The binding of down-regulated genes (LYZ and GBP1) with growth factor GM-CSF using docking and MD simulation techniques, indicated that GM-CSF has the potential to alleviate the repressed hematopoiesis in the term LBW newborns. Conclusion Our study revealed that DEHGs belonged to erythroid and myeloid-specific lineages and may serve as potential targets for improving hematopoiesis in term LBW newborns to help build up their weak immune defense against life-threatening infections.

中文翻译:

通过系统基因组学方法鉴定足月低出生体重新生儿差异表达的造血相关基因

背景 低出生体重 (LBW)(出生体重 <2.5 公斤)新生儿在围产期与感染、发病率和死亡率的高风险相关。足月 LBW 新生儿的先天免疫反应受损和造血分化低效导致我们评估造血的基因表达状态。材料和方法 在本研究中,我们通过使用 gplots 和 RcolorBrewer 的层次聚类算法将我们的 LBW 正常出生体重 (NBW) 新生儿的微阵列数据集与两个参考数据集进行比较,以识别造血干细胞基因及其在 LBW 新生儿中的差异表达R中的包结果比较分析显示108个差异表达的造血基因(DEHG),其中79个基因被上调,与 NBW 对应物相比,LBW 新生儿中有 29 个基因被下调。此外,蛋白质-蛋白质相互作用、功能注释和通路分析表明,上调基因主要参与细胞增殖和分化、MAPK信号和Rho GTPases信号,下调基因主要参与细胞增殖和调节、免疫系统调节、造血细胞谱系和 JAK-STAT 通路。使用对接和 MD 模拟技术将下调基因(LYZ 和 GBP1)与生长因子 GM-CSF 结合,表明 GM-CSF 具有减轻 LBW 新生儿受抑制的造血功能的潜力。
更新日期:2020-01-01
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