Analysis of Hub Genes Involved in Distinction Between Aged and Fetal Bone Marrow Mesenchymal Stem Cells by Robust Rank Aggregation and Multiple Functional Annotation Methods
Stem cells from fetal tissue protect against aging and possess greater proliferative capacity than their adult counterparts. These cells can more readily expand in vitro and senesce later in culture. However, the underlying molecular mechanisms for these differences are still not fully understood. I...
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| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2020.573877/full |
| _version_ | 1818350626166276096 |
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| author | Xiaoyao Liu Mingjing Yin Xinpeng Liu Junlong Da Kai Zhang Xinjian Zhang Lixue Liu Jianqun Wang Han Jin Zhongshuang Liu Bin Zhang Bin Zhang Ying Li |
| author_facet | Xiaoyao Liu Mingjing Yin Xinpeng Liu Junlong Da Kai Zhang Xinjian Zhang Lixue Liu Jianqun Wang Han Jin Zhongshuang Liu Bin Zhang Bin Zhang Ying Li |
| author_sort | Xiaoyao Liu |
| collection | DOAJ |
| description | Stem cells from fetal tissue protect against aging and possess greater proliferative capacity than their adult counterparts. These cells can more readily expand in vitro and senesce later in culture. However, the underlying molecular mechanisms for these differences are still not fully understood. In this study, we used a robust rank aggregation (RRA) method to discover robust differentially expressed genes (DEGs) between fetal bone marrow mesenchymal stem cells (fMSCs) and aged adult bone marrow mesenchymal stem cells (aMSCs). Multiple methods, including gene set enrichment analysis (GSEA), Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation of the robust DEGs, and the results were visualized using the R software. The hub genes and other genes with which they interacted directly were detected by protein–protein interaction (PPI) network analysis. Correlation of gene expression was measured by Pearson correlation coefficient. A total of 388 up-regulated and 289 down-regulated DEGs were identified between aMSCs and fMSCs. We found that the down-regulated genes were mainly involved in the cell cycle, telomerase activity, and stem cell proliferation. The up-regulated DEGs were associated with cell adhesion molecules, extracellular matrix (ECM)–receptor interactions, and the immune response. We screened out four hub genes, MYC, KIF20A, HLA-DRA, and HLA-DPA1, through PPI-network analysis. The MYC gene was negatively correlated with TXNIP, an age-related gene, and KIF20A was extensively involved in the cell cycle. The results suggested that MSCs derived from the bone marrow of an elderly donor present a pro-inflammatory phenotype compared with that of fMSCs, and the HLA-DRA and HLA-DPA1 genes are related to the immune response. These findings provide new insights into the differences between aMSCs and fMSCs and may suggest novel strategies for ex vivo expansion and application of adult MSCs. |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-13T18:24:50Z |
| publishDate | 2020-12-01 |
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| spelling | doaj.art-18e3d25e272649f5ae0e2340976fdd7d2022-12-21T23:35:37ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-12-011110.3389/fgene.2020.573877573877Analysis of Hub Genes Involved in Distinction Between Aged and Fetal Bone Marrow Mesenchymal Stem Cells by Robust Rank Aggregation and Multiple Functional Annotation MethodsXiaoyao Liu0Mingjing Yin1Xinpeng Liu2Junlong Da3Kai Zhang4Xinjian Zhang5Lixue Liu6Jianqun Wang7Han Jin8Zhongshuang Liu9Bin Zhang10Bin Zhang11Ying Li12Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaInstitute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaInstitute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaInstitute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaInstitute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaInstitute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaInstitute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaInstitute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaInstitute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaInstitute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaInstitute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaHeilongjiang Academy of Medical Sciences, Harbin, ChinaInstitute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaStem cells from fetal tissue protect against aging and possess greater proliferative capacity than their adult counterparts. These cells can more readily expand in vitro and senesce later in culture. However, the underlying molecular mechanisms for these differences are still not fully understood. In this study, we used a robust rank aggregation (RRA) method to discover robust differentially expressed genes (DEGs) between fetal bone marrow mesenchymal stem cells (fMSCs) and aged adult bone marrow mesenchymal stem cells (aMSCs). Multiple methods, including gene set enrichment analysis (GSEA), Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation of the robust DEGs, and the results were visualized using the R software. The hub genes and other genes with which they interacted directly were detected by protein–protein interaction (PPI) network analysis. Correlation of gene expression was measured by Pearson correlation coefficient. A total of 388 up-regulated and 289 down-regulated DEGs were identified between aMSCs and fMSCs. We found that the down-regulated genes were mainly involved in the cell cycle, telomerase activity, and stem cell proliferation. The up-regulated DEGs were associated with cell adhesion molecules, extracellular matrix (ECM)–receptor interactions, and the immune response. We screened out four hub genes, MYC, KIF20A, HLA-DRA, and HLA-DPA1, through PPI-network analysis. The MYC gene was negatively correlated with TXNIP, an age-related gene, and KIF20A was extensively involved in the cell cycle. The results suggested that MSCs derived from the bone marrow of an elderly donor present a pro-inflammatory phenotype compared with that of fMSCs, and the HLA-DRA and HLA-DPA1 genes are related to the immune response. These findings provide new insights into the differences between aMSCs and fMSCs and may suggest novel strategies for ex vivo expansion and application of adult MSCs.https://www.frontiersin.org/articles/10.3389/fgene.2020.573877/fullbone marrow mesenchymal stem cellfetal stem celladult setm cellrobust rank aggregationhub genes |
| spellingShingle | Xiaoyao Liu Mingjing Yin Xinpeng Liu Junlong Da Kai Zhang Xinjian Zhang Lixue Liu Jianqun Wang Han Jin Zhongshuang Liu Bin Zhang Bin Zhang Ying Li Analysis of Hub Genes Involved in Distinction Between Aged and Fetal Bone Marrow Mesenchymal Stem Cells by Robust Rank Aggregation and Multiple Functional Annotation Methods Frontiers in Genetics bone marrow mesenchymal stem cell fetal stem cell adult setm cell robust rank aggregation hub genes |
| title | Analysis of Hub Genes Involved in Distinction Between Aged and Fetal Bone Marrow Mesenchymal Stem Cells by Robust Rank Aggregation and Multiple Functional Annotation Methods |
| title_full | Analysis of Hub Genes Involved in Distinction Between Aged and Fetal Bone Marrow Mesenchymal Stem Cells by Robust Rank Aggregation and Multiple Functional Annotation Methods |
| title_fullStr | Analysis of Hub Genes Involved in Distinction Between Aged and Fetal Bone Marrow Mesenchymal Stem Cells by Robust Rank Aggregation and Multiple Functional Annotation Methods |
| title_full_unstemmed | Analysis of Hub Genes Involved in Distinction Between Aged and Fetal Bone Marrow Mesenchymal Stem Cells by Robust Rank Aggregation and Multiple Functional Annotation Methods |
| title_short | Analysis of Hub Genes Involved in Distinction Between Aged and Fetal Bone Marrow Mesenchymal Stem Cells by Robust Rank Aggregation and Multiple Functional Annotation Methods |
| title_sort | analysis of hub genes involved in distinction between aged and fetal bone marrow mesenchymal stem cells by robust rank aggregation and multiple functional annotation methods |
| topic | bone marrow mesenchymal stem cell fetal stem cell adult setm cell robust rank aggregation hub genes |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2020.573877/full |
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