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微阵列分析鉴定成骨分化过程中差异基因表达的关键途径和相互作用网络。

Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation.

机构信息

Department of Molecular Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

出版信息

Hum Genomics. 2020 Nov 25;14(1):43. doi: 10.1186/s40246-020-00293-1.

Abstract

BACKGROUND

Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells that can differentiate into three lineages. They are suitable sources for cell-based therapy and regenerative medicine applications. This study aims to evaluate the hub genes and key pathways of differentially expressed genes (DEGs) related to osteogenesis by bioinformatics analysis in three different days. The DEGs were derived from the three different days compared with day 0.

RESULTS

Gene expression profiles of GSE37558 were obtained from the Gene Expression Omnibus (GEO) database. A total of 4076 DEGs were acquired on days 8, 12, and 25. Gene ontology (GO) enrichment analysis showed that the non-canonical Wnt signaling pathway and lipopolysaccharide (LPS)-mediated signaling pathway were commonly upregulated DEGs for all 3 days. KEGG pathway analysis indicated that the PI3K-Akt and focal adhesion were also commonly upregulated DEGs for all 3 days. Ten hub genes were identified by CytoHubba on days 8, 12, and 25. Then, we focused on the association of these hub genes with the Wnt pathways that had been enriched from the protein-protein interaction (PPI) by the Cytoscape plugin MCODE.

CONCLUSIONS

These findings suggested further insights into the roles of the PI3K/AKT and Wnt pathways and their association with osteogenesis. In addition, the stem cell microenvironment via growth factors, extracellular matrix (ECM), IGF1, IGF2, LPS, and Wnt most likely affect osteogenesis by PI3K/AKT.

摘要

背景

成人骨髓间充质干细胞(BM-MSCs)是多能干细胞,可分化为三个谱系。它们是细胞治疗和再生医学应用的合适来源。本研究旨在通过生物信息学分析评估与成骨相关的差异表达基因(DEGs)的关键基因和关键途径,这些 DEGs 是从与第 0 天相比的第 3、8、12 和 25 天获得的。

结果

从基因表达综合数据库(GEO)中获得了 GSE37558 的基因表达谱。在第 8、12 和 25 天共获得了 4076 个 DEGs。基因本体论(GO)富集分析表明,非经典 Wnt 信号通路和脂多糖(LPS)介导的信号通路是所有 3 天都上调的 DEGs。KEGG 通路分析表明,PI3K-Akt 和黏附斑也是所有 3 天都上调的 DEG。通过 CytoHubba 在第 8、12 和 25 天鉴定了 10 个关键基因。然后,我们通过 Cytoscape 插件 MCODE 从蛋白质-蛋白质相互作用(PPI)中富集的 Wnt 途径来关注这些关键基因与 Wnt 途径的关联。

结论

这些发现进一步深入了解了 PI3K/AKT 途径和 Wnt 途径及其与成骨的关系。此外,通过生长因子、细胞外基质(ECM)、IGF1、IGF2、LPS 和 Wnt 的干细胞微环境可能通过 PI3K/AKT 影响成骨。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b484/7687700/bcaf668f0c4a/40246_2020_293_Fig1_HTML.jpg

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