RNA accumulation in aged endothelial cells links an interferon gene signature to cellular senescence
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE160356 | GEO | 2023/10/27
REPOSITORIES: GEO
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Project description:RNA-seq was performed on 4-week high glucose (25mM D-glucose) treated human retinal microvascular endothelial cells (HRMECs) and control (5mM D-glucose) passage-matched cells.
2022-09-20 | GSE199548 | GEO
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: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. Keywords: Replicative senescence, time course
2008-07-29 | GSE9593 | GEO
Project description:To identify the most suitable reference genes for ECFC senescence studies, we analysed a microarray dataset, which compared the gene expression between proliferating and senescent ECFCs. In addition to replicative senescence, the data included X-ray-induced and Etoposide-induced senescence. We used the geNorm algorithm to identify the most stable genes across all studied conditions.
2019-03-27 | GSE125792 | GEO
Project description:Transcriptional profiling of normal human diploid fibroblasts(TIG-3) comparing late passage with early passage. Total RNA was isolated using TRIzol reagent and were analyzed using the human 3D-Gene DNA chip (Toray) that contains 25000 genes. The genome wide transcriptional response of senescent cells(more than 70 population doublings)(Replicative) were compared to that of proliferating cells(less than 40 population doublings)(Young).
2014-04-10 | E-GEOD-49860 | biostudies-arrayexpress
Project description:Purpose: Transcriptomics analysis provides a genome-wide digital gene expression profile, which reveals the regulation of gene transcription at the overall level. This study aimed to investigate the underlying mechanism of carnosol against t-BHP-induced Human retinal microvascular endothelial cells (HRMECs) oxidative stress injury. Methods: HRMECs were treated with 10 μM carnosol for 24 h, followed by 300 μM t-BHP for 4 h to simulate the oxidative stress environment in vitro. Oligo dT was used to generate the cDNA library. After constructing the cDNA library, the quality of the library was detected with Agilent biological analyzer, and the cDNA was sequenced with Illumina. Conclusions: Our data provide a systematic perspective for the mechanism of carnosol against HRMECs oxidative stress injury, which lay a foundation for further study on carnosol.
2022-03-31 | GSE186471 | GEO
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:The aim of the present study was to provide a comprehensive characterization of whole genome DNA methylation patterns in replicative and ionizing irradiation- or doxorubicin-induced premature senescence, exhaustively exploring epigenetic modifications in three different human cell types: in somatic diploid skin fibroblasts and in bone marrow- and adipose-derived mesenchymal stem cells. With CpG-wise differential analysis three epigenetic signatures were identified: a) cell type- and treatment-specific signature; b) cell type-specific senescence-related signature; and c) cell type-transversal replicative senescence-related signature. Cluster analysis revealed that only replicatively senescent cells created a distinct group reflecting notable alterations in the DNA methylation patterns accompanying this cellular state. Replicative senescence-associated epigenetic changes seemed to be of such an extent that they surpassed interpersonal dissimilarities. Enrichment in pathways linked to the nervous system and involved in the neurological functions was shown after pathway analysis of genes involved in the cell type-transversal replicative senescence-related signature. Although DNA methylation clock analysis provided no statistically significant evidence on epigenetic age acceleration related to senescence, a persistent trend of increased biological age in replicatively senescent cultures of all three cell types was observed. Overall, this work indicates the heterogeneity of senescent cells depending on the tissue of origin and the type of senescence inducer that could be putatively translated to a distinct impact on tissue homeostasis.
2023-03-20 | GSE227160 | GEO
Project description:Senescent passage 26 fibroblasts compared to proliferating passage 8 fibroblasts Keywords: Senescent vs. Proliferating
2007-01-24 | GSE6762 | GEO
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 Keywords: ordered
2004-03-01 | GSE687 | GEO