Similar Datasets
Project description:Obesity is a health problem characterized by large expansion of adipose tissue. During this expansion, genotoxic stressors can be accumulated and negatively affect the Mesenchymal Stem Cells (MSCs) of adipose tissue. Due to the oxidative stress generated by these genotoxic stressors, senescence phenotype might be observed in adipose tissue MSCs. Senescent MSCs lose their proliferations and differentiation properties and secrete senescence-associated molecules to their niche thus triggering senescence for the rest of the tissue. Accumulation of senescent cells in adipose tissue results in decreased tissue regeneration and functional impairment not only in the close vicinity but also in the other tissues. Here we hypothesized that declined tissue regeneration might be associated with loss of stemness in MSCs population. We analyzed the expression of several stemness genes in adipose tissue MSCs of high-fat diet and normal diet mice models. Since the MSCs population covers a small percentage of the pluripotent stem cells, a role in proliferation and tissue regeneration, we measured the percentage of these cells via TRA-1-60 surface antigen. Additionally, by conducting a shotgun proteomic approach using LC-MS/MS, whole cell proteome of the adipose tissue MSCs of high-fat diet and normal diet mice were analyzed and identified proteins were evaluated via Gene Ontology and PPI network analysis. MSCs of obese mice showed senescent phenotype and altered cell cycle distribution due to a hostile environment with oxidative stress in adipose tissue where they reside. Additionally, the number of pluripotent markers expressing cells declined in the MSC population of the high-fat diet mice. Gene expression analysis evidenced the loss of stemness with a decrease in the expression of stemness-associated genes. Of the proteomic comparison of the normal and the high-fat diet group, MSCs revealed that stemness-associated molecules were decreased while inflammation and senescence-associated phenotypes emerged in obese mice MSCs. Our results showed us that the MSCs of adipose tissue may lose their stemness properties due to obesity-associated stress conditions.
2024-10-17 | PXD050811 | Pride
Project description:Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cells (iPSCs) assimilate towards a ground-state and may therefore give rise to more standardized cell preparations. We reprogrammed bone marrow MSCs into iPSCs which were subsequently re-differentiated towards MSCs. These iPS-MSCs revealed similar morphology, immunophenotype, in vitro differentiation potential, and gene expression profiles as primary MSCs. DNA methylation (DNAm) profiles of iPSCs maintained some donor-specific characteristics, whereas tissue-specific, senescence-associated, and age-related DNAm patterns were erased during reprogramming. iPS-MSCs reacquired senescence-associated DNAm during culture expansion but they remained rejuvenated with regard to age-related DNAm. Overall, iPS-MSCs and MSCs are similar in function but differ in their epigenetic makeup. 8 samples were hybridized to the GeneChip Human Gene 1.0 ST Array (Affymetrix)
2014-09-24 | E-GEOD-54766 | biostudies-arrayexpress
Project description:Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cells (iPSCs) assimilate towards a ground-state and may therefore give rise to more standardized cell preparations. We reprogrammed bone marrow MSCs into iPSCs which were subsequently re-differentiated towards MSCs. These iPS-MSCs revealed similar morphology, immunophenotype, in vitro differentiation potential, and gene expression profiles as primary MSCs. DNA methylation (DNAm) profiles of iPSCs maintained some donor-specific characteristics, whereas tissue-specific, senescence-associated, and age-related DNAm patterns were erased during reprogramming. iPS-MSCs reacquired senescence-associated DNAm during culture expansion but they remained rejuvenated with regard to age-related DNAm. Overall, iPS-MSCs and MSCs are similar in function but differ in their epigenetic makeup. 12 samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip
2014-09-24 | E-GEOD-54767 | biostudies-arrayexpress
Project description:Replicative senescence hampers application of mesenchymal stromal cells (MSCs) because it limits culture expansion, impairs differentiation potential, and hinders reliable standardization of cell products. MSCs can be rejuvenated by reprogramming into induced pluripotent stem cells (iPSCs), which is associated with complete erasure of age- and senescence-associated DNA methylation (DNAm) patterns. However, this process is also associated with erasure of cell-type and tissue-specific epigenetic characteristics that are not recapitulated upon re-differentiation towards MSCs. In this study, we therefore followed the hypothesis that overexpression of pluripotency factors under culture conditions that do not allow full reprogramming might reset senescence-associated changes without entering a pluripotent state. MSCs were transfected with episomal plasmids and either successfully reprogrammed into iPSCs or cultured in different media with continuous passaging every week. Overexpression of pluripotency factors without reprogramming did neither prolong culture expansion nor ameliorate molecular and epigenetic hallmarks of senescence. Notably, transfection resulted in immortalization of one cell preparation with gain of large parts of the long arm of chromosome 1. Taken together, premature termination of reprogramming does not result in rejuvenation of MSCs and harbours the risk of transformation. This approach is therefore not suitable to rejuvenate cells for cellular therapy.
2019-05-21 | GSE115666 | GEO
Project description:Stem cell therapy requires massive scale homogeneous stem cells under strictly qualification control. However, Prolonged ex vivo expansion impairs the biological functions and results in senescence of mesenchymal stem cells (MSCs). We investigated the function of CTDSPL in premature senescence process of MSCs and clarified that miR-18a-5p played a prominent role in preventing senescence of long-term cultured MSCs and promoting the self-renew ability of MSCs. Inhibition of miR-18a-5p promoted the expression of CTDSPL and induced premature senescence of MSCs. Continuous overexpression of miR-18a-5p improved self-renewal of MSCs by reduced ROS level, increased expression of Oct4 and Nanog, promoted growth rate and differentiation capability. We reported for the first time the dynamic interaction of miR-18a-5p and CTDSPL is crucial for stem cell senescence.
2022-09-04 | GSE212185 | GEO
Project description:Cancer therapy induced effects on mesenchymal stem cells
| PRJNA1041783 | ENA
Project description:we attempted to identify the genetic changes in the remaining MSCs after BPTES treatment and identified senescence-related candidate genes that recovered after BPTES treatment. The transcriptomes of U-MSCs and rS-MSCs were analyzed to determine the genetic significance of replicative senescence in WJ-MSCs
2024-09-26 | GSE250218 | GEO
Project description:Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cells (iPSCs) assimilate towards a ground-state and may therefore give rise to more standardized cell preparations. We reprogrammed bone marrow MSCs into iPSCs which were subsequently re-differentiated towards MSCs. These iPS-MSCs revealed similar morphology, immunophenotype, in vitro differentiation potential, and gene expression profiles as primary MSCs. DNA methylation (DNAm) profiles of iPSCs maintained some donor-specific characteristics, whereas tissue-specific, senescence-associated, and age-related DNAm patterns were erased during reprogramming. iPS-MSCs reacquired senescence-associated DNAm during culture expansion but they remained rejuvenated with regard to age-related DNAm. Overall, iPS-MSCs and MSCs are similar in function but differ in their epigenetic makeup.
2014-09-24 | GSE54767 | GEO
Project description:Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cells (iPSCs) assimilate towards a ground-state and may therefore give rise to more standardized cell preparations. We reprogrammed bone marrow MSCs into iPSCs which were subsequently re-differentiated towards MSCs. These iPS-MSCs revealed similar morphology, immunophenotype, in vitro differentiation potential, and gene expression profiles as primary MSCs. DNA methylation (DNAm) profiles of iPSCs maintained some donor-specific characteristics, whereas tissue-specific, senescence-associated, and age-related DNAm patterns were erased during reprogramming. iPS-MSCs reacquired senescence-associated DNAm during culture expansion but they remained rejuvenated with regard to age-related DNAm. Overall, iPS-MSCs and MSCs are similar in function but differ in their epigenetic makeup.
2014-09-24 | GSE54766 | GEO
Project description:Senotherapeutics are new drugs, which can modulate senescence phenomena within tissues and reduces the onset of age-related pathologies. Senotherapeutics are divided in senolytics and senomorphics. The senolytics kill selectively senescent cells, while the senomorphics may delay or block the onset of senescence. Metformin is used for treatment of diabetes since several decades. Recently, it has been evidenced that metformin may have anti-aging properties by preventing DNA damage and inflammation. We evaluated the senomorphics effect of metformin on the biology human adipose mesenchymal stromal cells (MSCs) treated for six weeks with therapeutic doses of metformin. The study was combined with proteome analysis of changes occurring in MSCs intracellular and secretome protein composition, this to identify molecular pathways associated with the observed biological phenomena. The metformin reduced the replicative senescence and cell death phenomena, which are associated with prolonged in vitro cultivation. The continuous metformin supplementation delayed/reduced the impairment of MSC functions as evidenced by the presence of specific pathways in metformin treated samples: i) the alpha-adrenergic signaling, which contributes to regulation of MSCs physiological secretory activity; the signaling pathway associated with MSCs detoxification activity; the aspartate degradation pathway for optimal energy production. The senomorphics function of metformin seemed related to its reactive oxygen species (ROS) scavenging activity. In metformin treated samples, the CEBPA, TP53 and USF1 transcription factors appeared implicated in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) involved in blocking ROS.
2022-02-15 | PXD028349 | Pride