scholarly journals 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

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyao Liu ◽  
Mingjing Yin ◽  
Xinpeng Liu ◽  
Junlong Da ◽  
Kai Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Immune Response ◽  
Mesenchymal Stem Cells ◽  
Functional Annotation ◽  
Rank Aggregation ◽  
Ppi Network ◽  
Hub Genes ◽  
Marrow Mesenchymal Stem Cells

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.

scholarly journals Cholesterol Retards Senescence in Bone Marrow Mesenchymal Stem Cells by Modulating Autophagy and ROS/p53/p21Cip1/Waf1Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Mingyu Zhang ◽  
Yue Du ◽  
Renzhong Lu ◽  
You Shu ◽  
Wei Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cellular Senescence ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
Marrow Mesenchymal Stem Cells ◽  
Dose Dependent ◽  
Increased Activity

In the present study, we demonstrated that bone marrow mesenchymal stem cells (BMSCs) of the 3rd passage displayed the senescence-associated phenotypes characterized with increased activity of SA-β-gal, altered autophagy, and increased G1 cell cycle arrest, ROS production, and expression of p53 andp21Cip1/Waf1compared with BMSCs of the 1st passage. Cholesterol (CH) reduced the number of SA-β-gal positive cells in a dose-dependent manner in aging BMSCs induced by H2O2and the 3rd passage BMSCs. Moreover, CH inhibited the production of ROS and expression of p53 andp21Cip1/Waf1in both cellular senescence models and decreased the percentage of BMSCs in G1 cell cycle in the 3rd passage BMSCs. CH prevented the increase in SA-β-gal positive cells induced by RITA (reactivation of p53 and induction of tumor cell apoptosis, a p53 activator) or 3-MA (3-methyladenine, an autophagy inhibitor). Our results indicate that CH not only is a structural component of cell membrane but also functionally contributes to regulating cellular senescence by modulating cell cycle, autophagy, and the ROS/p53/p21Cip1/Waf1signaling pathway.

Human bone marrow mesenchymal stem cells suppress the proliferation of hepatic stellate cells by inhibiting the ubiquitination of p27

2017 ◽  
Vol 95 (6) ◽  
pp. 628-633 ◽  
Author(s):  
Liang Wang ◽  
Guang Bai ◽  
Fei Chen
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Cell Cycle Arrest ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Cycle Arrest ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) have considerable therapeutic potential for the treatment of end-stage liver disease. Previous studies have demonstrated that BMSCs secrete growth factors and cytokines that inactivate hepatic stellate cells (HSCs), which inhibited the progression of hepatic fibrosis. The aim of this study was to determine the mechanism by which BMSCs suppress the function of HSCs in fibrosis. Our results showed that co-culture of BMSCs and HSCs induced cell cycle arrest at the G10/G1 phase and cell apoptosis of HSCs, which finally inhibited the cell proliferation of HSCs. Consistent with the cell cycle arrest, co-culture of BMSCs and HSCs increased the abundance of the cell cycle protein p27. Mechanistically, we further uncovered that following the co-culture with BMSCs, the expression level of the E3 ligase S-phase kinase-associated protein 2 (SKP2) that is responsible for the ubiquitination of p27 was decreased, which attenuated the ubiquitination of p27 and increased the stability of p27 in HSCs. Collectively, our results indicated the potential involvement of the SKP2–p27 axis for the inhibitory effect of BSMCs on the cell proliferation of HSCs.

SRC3 expressed in bone marrow mesenchymal stem cells promotes the development of multiple myeloma

2019 ◽  
Vol 51 (12) ◽  
pp. 1258-1266 ◽  
Author(s):  
Jie Jin ◽  
Shidi Cheng ◽  
Yu Wang ◽  
Tao Wang ◽  
Dongfeng Zeng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Colony Formation ◽  
Apoptosis Pathway ◽  
Promote Cell Proliferation ◽  
Mitochondrial Apoptosis Pathway ◽  
Marrow Mesenchymal Stem Cells

Abstract SRC3 plays critical roles in various biological processes of diseases, including proliferation, apoptosis, migration, and cell cycle arrest. However, the effect of SRC3 expression in mesenchymal stem cells (MSCs) on multiple myeloma (MM) is not clear yet. In our study, MSCs (MSC-SRC3, MSC-SRC3−/−) and MM cells were co-cultured in a direct or indirect way. The proliferation of MM cells was studied by CCK-8 and colony formation assays. The apoptosis and cell cycle of MM cells were detected by flow cytometry. In addition, the expressions of proteins in MM cells were detected by western blot analysis and the secretions of cytokines were measured by ELISA. Our data showed that the expression of SRC3 in bone marrow mesenchymal stem cells (BM-MSCs) could promote cell proliferation and colony formation of MM cells through accelerating the transformation of the G1/S phase, no matter what kind of culture method was adopted. Meanwhile, SRC3 expressed in BM-MSCs could inhibit the apoptosis of MM cells through the caspase apoptosis pathway and mitochondrial apoptosis pathway. Moreover, SRC3 could enhance the adhesion ability of MM cells through up-regulating the expression of adhesion molecules including CXCL4, ICAM1, VLA4, and syndecan-1. SRC3 also played a regulatory role in the progress of MM through the NF-κB and PI-3K/Akt pathways. SRC3 expressed in MSCs was found to promote the growth and survival of MM cells, while SRC3 silencing in MSCs could inhibit the development of MM. These results would be useful for developing a more effective new strategy for MM treatment.

Effect of miR-124 on the Biological Characteristics of Bone Marrow Mesenchymal Stem Cells in Tumor Microenvironment

2020 ◽  
Vol 10 (2) ◽  
pp. 151-156
Author(s):  
Linfu He ◽  
XiaoyanHe ◽  
Xiaocui Liu ◽  
Wenjing Shi ◽  
PeiXu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Glioma Cells ◽  
Biological Characteristics ◽  
Brain Glioma ◽  
Marrow Mesenchymal Stem Cells

miR-124 affects migration and differentiation of mesenchymal stem cells (MSCs), but its role in bone marrow mesenchymal stem cells (BMSCs) in tumor microenvironment remain unclear. Therefore, our study aims to assess miR-124’s role in BMSCs in glioma microenvironment. BMSCs were isolated and co-cultured with glioma cells using Transwell chamber and then transfected with miR-124 mimic/NC followed by analysis of BMSCs biological characteristics (cell proliferation by CCK8, miR-124 level by Real-time PCR, cell cycle and apoptosis by flow cytometry, and cell migration by Transwell). There were significant differences of cell proliferation, migration, apoptosis and cell cycle in BMSCs group compared to co-culture and co-culture+ miR-NC group (P < 0.05), without no difference compared to co-culture + miR-124 group. In addition, co-culture + miR-124 also showed significant differences of BMSCs' biological characteristics (P < 0.05). miR-124 can alter the biological characteristics of BMSCs in the tumor microenvironment simulated by C6 brain glioma cells.

scholarly journals Bone Marrow Mesenchymal Stem Cells Loaded With an Oncolytic Adenovirus Suppress the Anti-adenoviral Immune Response in the Cotton Rat Model

2010 ◽  
Vol 18 (10) ◽  
pp. 1846-1856 ◽  
Author(s):  
Atique U Ahmed ◽  
Cleo E Rolle ◽  
Matthew A Tyler ◽  
Yu Han ◽  
Sadhak Sengupta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Immune Response ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Oncolytic Adenovirus ◽  
Cotton Rat ◽  
Marrow Mesenchymal Stem Cells

scholarly journals High-Dose 111In Induces G1 Cell Cycle Arrest and Cell Death in Rat Bone Marrow Mesenchymal Stem Cells

2012 ◽  
Vol 46 (2) ◽  
pp. 81-88 ◽  
Author(s):  
Bok-Nam Park ◽  
Wooyoung Shim ◽  
Young Hwan Ahn ◽  
Jae-Ho Lee ◽  
Young-Sil An ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cell Death ◽  
Mesenchymal Stem Cells ◽  
High Dose ◽  
Cycle Arrest ◽  
Marrow Mesenchymal Stem Cells ◽  
G1 Cell Cycle Arrest ◽  
Rat Bone
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