Cellular Aging of Mesenchymal Stem Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE9593 | GEO | 2008/07/29
SECONDARY ACCESSION(S): PRJNA103435
REPOSITORIES: GEO
Similar Datasets
Project description:To determine miRNA expression changes during in vitro senescence of mesenchymal stem cells (MSC) we have analyzed differential expression of the corresponding early passage (P2) and senescent passage (PX). Keywords: miRNA, senescence, mesenchymal stromal cells, mesenchymal stem cells, MSC
2008-07-29 | GSE9664 | GEO
Project description:To determine gene expression changes during in vitro senescence of MSC we have analyzed differential expression of the corresponding early passage (P2) and senescent passage (PX). There were global changes in the gene expression profile that were reproducible in three independent donor samples. Experiment Overall Design: Mesenchymal Stem Cells (MSC) were isolated from human bone marrow (BM) as described before (Wagner et al., 2005, Exp Hematol, 33, 1402-1416; Wagner et al., Exp Hematol, 34, 536-548). Cells were always replated when grown to confluency. A sample for RNA isolation was taken at every passage until the cells finally became senescent: they became much larger with irregular and flat shape. The nucleus became more circumscribed in phase contrast microscopy. The cytoplasm began to be granular with many inclusions and there was more cell debris. Global gene expression profiles were analyzed to determine molecular changes between corresponding early passage (P2) and senescent passage (PX) in three donor samples. In addition we have analyzed different passages of donor 1 (P2, P3, P4, P5, P6, P7, P8, P10, and P11) to determine changes in the course of cellular aging. Data were median normalized and compared to P2 of the corresponding donor sample.
2008-10-20 | E-GEOD-9593 | biostudies-arrayexpress
Project description:In this study, we have analyzed DNA methylation changes upon long-term culture and aging of MSC by using the HumanMethylation27 BeadChip assessing 27,578 unique CpG sites. Cells were taken from bone marrow aspirates from iliac crest (BM) of healthy donors or from the caput femoris (HIP) of elderly patients that received femoral head prosthesis.Overall, the methylation pattern was maintained throughout both long-term culture and aging but highly significant differences were observed at specific CpG sites. Notably, methylation changes in MSC were related in long-term culture and aging in vivo. Mesenchymal stromal cells (MSC) were isolated from human bone marrow as described before (Wagner et al., 2006, Exp Hematol, 34, 536-548; Wagner et al.,2008, PLoS One 21;3(5):e2213.; Wagner et al., PLoS One. 2009 Jun 9;4(6):e5846.) Cells were always replated when grown to confluency. A sample for DNA isolation was taken at every passage until the cells finally became senescent. For methylation profiles upon long-term culture we used the samples of early passage (P2) and senescent passage (PX). For methylation profiles upon aging we have only used the samples of passage 2 of younger and elderly donors. Gene expression data of these samples have been previously deposited unter GSE9593 and GSE12274.
2010-05-14 | E-GEOD-17448 | biostudies-arrayexpress
Project description:<p><strong>BACKGROUND:</strong> Periodontal ligament mesenchymal stem cells (PDLSCs) are a promising cell resource for cell-based regenerative medicine in dentistry. PDLSCs inevitably acquire a senescent phenotype after prolonged in vitro expansion, and the key regulators of cells during replicative senescence remain unclear.</p><p><strong>METHODS:</strong> We cultured periodontal ligament stem cells to passages 4, 10 and 20 (P4, P10, P20). The senescent phenotypes, proliferation and migration ability of PDLSCs (P4, P10, P20) were detected, and non-targeted metabonomic sequencing was performed. We treated PDLSCs with AICAR and detected the expression of FOXO1, FOXO3a, FOXO6 and AMPK phosphorylation (p-AMPK) levels of replicating senescent PDLSCs to explore the correlation between the metabolic changes and the AMPK pathway.</p><p><strong>RESULTS:</strong> Immunofluorescence staining of γ-H2AX, β-galactosidase staining, cell scratch test and qPCR were performed to confirm the occurrence of replicative senescence in PDLSCs during passaging. Three groups of cells at passage 4 (P4), passage 10 (P10) and passage 20 (P20) were collected for non-targeted metabolomics analysis. Metabonomic sequencing showed that the metabolism of replicative senescence in PDLSCs varied significantly. In particular, the content of fatty acid metabolites decreased with senescence, including capric acid, stearic acid, myristic acid and dodecanoic acid. KEGG pathway analysis showed that the AMPK signaling pathway was closely related to AMP levels. The AMP:ATP ratio increased in senescent PDLSCs; however, the levels of p-AMPK and the profile of FOXO1 and FOXO3a, which are downstream of the AMPK signaling pathway, decreased with senescence. We treated PDLSCs with AICAR, an activator of the AMPK pathway, and the phosphorylated AMPK level at P20 PDLSCs was partially restored. </p><p><strong>CONCLUSION:</strong> In summary, our study suggests that the metabolic process of PDLSCs is active in the early stage of senescence, prefers to consume fatty acids, and is attenuated in the later stages of senescence. AMP accumulates in replicative senescent PDLSCs; however, the sensitivity of AMPK phosphorylation sites is impaired, causing senescent PDLSCs to fail to respond to changes in energy metabolism. Our findings provide a new basis for the clinical application of periodontal ligament stem cells.</p>
2022-11-15 | MTBLS4568 | MetaboLights
Project description:Senescent cells secrete many molecules, which contribute to the prevention of cancer progression. We induced MSC senescence by oxidative stress, DNA damage, and replicative exhaustion. The first two are considered inducers of acute senescence while extensive proliferation triggers replicative senescence also named chronic senescence. We cultivated cancer cells in the presence of acute and chronic senescent MSC conditioned media and evaluated proliferation, DNA damage, apoptosis and senescence.
2018-10-25 | PXD003018 | Pride
Project description:Primary cells enter replicative senescence after a limited number of cell divisions. This process is associated with reproducible changes in DNA methylation (DNAm) at specific sites in the genome. The mechanism that drives senescence-associated DNAm changes remains unknown and may arise through drift in DNAm or through regulated, senescence dependent modifications at specific sites in the genome. In this study, we analyzed the reorganization of nuclear architecture and DNA methylation during long-term culture of human fibroblasts and mesenchymal stromal cells (MSCs). [RNA-seq] RNA was isolated from 1,000,000 cells of three MSC donors (59, 64, and 73 years old) at passage 4 and passage 13 using the miRNeasy Mini Kit (Qiagen). Gene expression profiles were analzyed by deep sequencing with IlluminaHiSeq 2000 technology with a read length of 50 bases at EMBL gene core facility (Heidelberg, Germany).
2015-03-26 | E-GEOD-59966 | biostudies-arrayexpress
Project description:RNA-seq was performed on early passage and senescent human retinal microvascular endothel cells (HRMECs), to determine transcriptomic changes. Replicative and Etoposide-induced senescent HRMECs senescence-associated gene signature and upregulation of an interferon related gene signature.
2023-10-27 | GSE160356 | GEO
Project description:Cells in culture undergo replicative senescence. In this study, we analyzed functional, genetic and epigenetic sequels of long‐term culture in human mesenchymal stem cells (MSC). Already within early passages the fibroblastoid colony‐ forming unit (CFU‐f) frequency and the differentiation potential of MSC declined significantly. Relevant chromosomal aberrations were not detected by karyotyping and SNP‐microarrays. Subsequently, we have compared DNA‐methylation profiles with the Infinium HumanMethylation27 Bead Array and the profiles differed markedly in MSC derived from adipose tissue and bone marrow. Notably, all MSC revealed highly consistent senescence‐associated modifications at specific CpG sites. These DNA‐methylation changes correlated with histone marks of previously published data sets, such as trimethylation of H3K9, H3K27 and EZH2 targets. Taken together, culture expansion of MSC has profound functional implications ‐ these are hardly reflected by genomic instability but they are associated with highly reproducible DNA‐methylation changes which correlate with repressive histone marks. Therefore replicative senescence seems to be epigenetically controlled. 8 samples of mesenchymal stem cells (MSC) from human adipose tissue
2011-10-27 | E-GEOD-26519 | biostudies-arrayexpress
Project description:To determine changes in gene expression in primary fibroblasts undergoing replicative senescence, a direct comparison between early passage proliferating cells and senescent cells was performed. Frozen stocks of the primary fibroblasts (HMF3) from which the lines HMF3A and HMF3Dwt were derived (O'Hare, PNAS:98, 2001) were serially passaged twice through to senescence to yield 2 independent sets of RNA. A third set of RNA was from a different female donor (F1068). The three different sets of RNA were put on 4 arrays each. Data is also provided for F1068 fibroblasts at late passage. Keywords = fibroblast Keywords = senescence Keywords = breast
2010-06-09 | E-GEOD-687 | biostudies-arrayexpress
Project description:Cells in culture undergo replicative senescence. In this study, we analyzed functional, genetic and epigenetic sequels of long‐term culture in human mesenchymal stem cells (MSC). Already within early passages the fibroblastoid colony‐ forming unit (CFU‐f) frequency and the differentiation potential of MSC declined significantly. Relevant chromosomal aberrations were not detected by karyotyping and SNP‐microarrays. Subsequently, we have compared DNA‐methylation profiles with the Infinium HumanMethylation27 Bead Array and the profiles differed markedly in MSC derived from adipose tissue and bone marrow. Notably, all MSC revealed highly consistent senescence‐associated modifications at specific CpG sites. These DNA‐methylation changes correlated with histone marks of previously published data sets, such as trimethylation of H3K9, H3K27 and EZH2 targets. Taken together, culture expansion of MSC has profound functional implications ‐ these are hardly reflected by genomic instability but they are associated with highly reproducible DNA‐methylation changes which correlate with repressive histone marks. Therefore replicative senescence seems to be epigenetically controlled.
2011-10-28 | GSE26519 | GEO