Project description:Cellular senescence is a dynamic tumor suppression mechanism that limits the proliferation of impaired cells, by executing a stable cell cycle arrest. Understanding the molecular pathways and regulatory circuits that are involved in the process of senescence is presently incomplete. In this study, we determined the changes in gene expression during the establishment of replicative senescence, by comparing the expression profiles of young and senescent human umbilical vein endothelial cells (HUVECs). Exploration of array data using ingenuity pathway analysis showed that genes involved in cell cycle regulation, cellular assembly and organization, DNA replication, recombination and repair were significantly down regulated during senescence.
Project description:By transcriptome analysis of IMR-90 human fibroblasts following oncogene-induced senescence (OIS) and replicative senescence (RS), we identified commonly regulated genes in both conditions.
Project description:MicroRNAs regulate various cellular processes. While several genes associated with replicative senescence have been described in endothelial cells, miRNAs that regulate these genes remain largely unknown. The present study was designed to identify miRNAs associated with replicative senescence and their target genes in HUVECs. We have employed Agilent Human MicroRNAs microarray platform to evaluate the expressions of 866 human miRNAs and 89 human viral miRNAs, based on Sanger miRNA database release 12.0 miRNA expression profiles were established for young and replicative senescent HUVECs
Project description:MicroRNAs regulate various cellular processes. While several genes associated with replicative senescence have been described in endothelial cells, miRNAs that regulate these genes remain largely unknown. The present study was designed to identify miRNAs associated with replicative senescence and their target genes in HUVECs. Gene profiling was established using the same RNA input as that used for miRNA profiing. We have employed Agilent Whole Human Genome microarray platform to evaluate the expressions of 19,596 human genes . Gene expression profiles were established for young and replicative senescent HUVECs
Project description:RNAseq analyses of NHEKs in replicative-like senescence, i.e. in growth arrest after about ten passages in culture, or in premature senescence induced by repeated UVB exposures (UVB-SIPS), at 3 days and at 5 days after the last UVB stress.
Project description:We stably infected IMR90 fibroblasts with lentiviral vectors expressing doxycycline-inducible TRF2dBdM or vector control. Cells were treated with 1mg/ml of doxycycline for 7 days to induce senescence in the cells expressing TRF2dBdM before collecting RNA. IMR90 cells, either young (passage 10, population doubling ~20) or old (passage 24, population doubling ~40-48) were also used as a model of replicative senescence. The transcriptomes were analyzed using RNA microarrays.
Project description:Telomere shortening in populations of human mammary epithelial cells (HMECs) that survive early replicative arrest (M0) by the inactivation of p16INK4A during cell culture on plastic dishes leads to a state of permanent replicative arrest termed senescence. While culture of HMECs on feeder layers abrogates M0 and p16INK4A inactivation, progressive telomere attrition in these cells also eventually results in permanent replicative arrest. Expression of telomerase prevents both senescence on plastic (S-P) and senescence on feeder layers (S-FL) in HMECs, as it does also in cultured primary human fibroblasts. We report here that the gene expression profiles of senescence in HMECs of the same lineage maintained under different culture conditions showed surprisingly little commonality. Moreover, neither of these senescence-associated profiles in HMECs resembles the profile for senescence in human fibroblasts. These results indicate that senescence-associated alterations in gene expression resulting from telomere attrition are affected by culture conditions as well as by cell origins, and argue that replicative senescence at the molecular level is a diverse rather than unique cellular process.