Yang'ou Wu1, Jing Yang2, Zexin Ai1, Miao Yu1, Jia Li3, Shengjiao Li4. 1. Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tongji University, Shanghai 200072, China; Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China. 2. Center for quantitative sciences, Vanderbilt University Medical Center, Nashville, TN, USA. 3. Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China; Department of Prosthodontics, School and Hospital of Stomatology, Tongji University, Shanghai 200072, China. Electronic address: lj2014@tongji.edu.cn. 4. Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tongji University, Shanghai 200072, China; Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China. Electronic address: 07824@tongji.edu.cn.
Abstract
BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells that can be widely used in stem cell therapy. However, few studies have revealed the potential mechanisms of the changes in aging MSC. MATERIALS AND METHODS: In this study, microarray data GSE35955 was downloaded from the Gene Expression Omnibus database. Then limma package in R was used to filtrate differentially expressed genes (DEGs), Transcription factors (TFs) were predicted by DCGL package. After predicting TFs, protein-protein interaction (PPI) network and TF-mediated transcriptional regulation network were constructed. The functional and pathway enrichment analysis of screened DEGs, hub genes and TFs were conducted by the DAVID. RESULTS: Totally 156 up-regulated DEGs and 343 down-regulated DEGs were obtained. 6 hub genes (CTNNB1, PPP2R1A, FYN, MAPK1, PIK3C2A and EP300) were obtained from PPI network. 11 TFs (CREB1, CUX1, EGR1, EP300, FOXC1, HSF2, MEF2A, PLAU, SP1, STAT1 and USF1) for DEGs were predicted and 2 highly scored co-expression relationships (EP300-PPP2R1A and STAT1-FOXC1) were acquired from the TF-mediated transcriptional regulation network. CONCLUSIONS: The discovery of the hub genes, TFs and pathways might contribute to the understanding of genetic and molecular functions of aging-related changes in MSC. Further validation studies on genes and TFs such as CTNNB1, FYN, PPP2R1A, MAPK1, EP300 and related biological processes and pathways, including adherens junction, DNA damage caused from oxidative stress, attribution of telomere, MSC differentiation and epigenetic regulation, are urgent for clinical prevention and treatment.
BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells that can be widely used in stem cell therapy. However, few studies have revealed the potential mechanisms of the changes in aging MSC. MATERIALS AND METHODS: In this study, microarray data GSE35955 was downloaded from the Gene Expression Omnibus database. Then limma package in R was used to filtrate differentially expressed genes (DEGs), Transcription factors (TFs) were predicted by DCGL package. After predicting TFs, protein-protein interaction (PPI) network and TF-mediated transcriptional regulation network were constructed. The functional and pathway enrichment analysis of screened DEGs, hub genes and TFs were conducted by the DAVID. RESULTS: Totally 156 up-regulated DEGs and 343 down-regulated DEGs were obtained. 6 hub genes (CTNNB1, PPP2R1A, FYN, MAPK1, PIK3C2A and EP300) were obtained from PPI network. 11 TFs (CREB1, CUX1, EGR1, EP300, FOXC1, HSF2, MEF2A, PLAU, SP1, STAT1 and USF1) for DEGs were predicted and 2 highly scored co-expression relationships (EP300-PPP2R1A and STAT1-FOXC1) were acquired from the TF-mediated transcriptional regulation network. CONCLUSIONS: The discovery of the hub genes, TFs and pathways might contribute to the understanding of genetic and molecular functions of aging-related changes in MSC. Further validation studies on genes and TFs such as CTNNB1, FYN, PPP2R1A, MAPK1, EP300 and related biological processes and pathways, including adherens junction, DNA damage caused from oxidative stress, attribution of telomere, MSC differentiation and epigenetic regulation, are urgent for clinical prevention and treatment.