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Project description:Genome wide mapping of H3K27ac in IMR90 oncogene induced senescence
| PRJNA610856 | ENA
Project description:This experiment was designed to study oncogene-induced senescence (OIS). To this end we generated a series of cell lines derived from normal human diploid fibroblasts IMR90 forced to express the catalytic subunit of telomerase (hTERT). This cells were then subjected to further manipulation by orderly introducing defined genetic elements by retroviral transduction. The first cell line generated was ITV, which was obtained from the original cell line (IMR90 with hTERT) after introducing an empty vector. Subsequently, we introduced Mek:ER, which is a switchable version of the Mek kinase, a relevant downstream effector of Ras signaling during Ras-induced senescence, to generate ITM cells. We further modified this cell line by introducing SV40 small-t antigen (ST), papillomavirus oncoproteins E6 and E7 (E6/E7) or the combination of both (E6/E7 and ST). In this manner, we obtained ITMST, ITME6E7 and ITME6E7ST respectively. This cellular system allow us to have a representation of the different steps into neoplastic transformation. ITM and ITMST cells respond to Mek activation by inducing OIS. ITME6E7 and ITME6E7ST cells do not enter OIS after Mek activation. Mek activation is achieved by treating all cell cultures with 4-hydroxytamoxifen (4OHT) at 100 nM, in the absence of serum, and for 3 days. The gene expression profile of ITV cells served as a reference for all the expression values obtained with the rest of the cell lines. Thus, we ended up with the expression profiles of two cell lines representing oncogene-induced senescence (ITM and ITMST), and two cell lines representing bypass of oncogene-induced senescence, plus a reference profile provided by ITV, the cell line from which all the other cell lines were derived. Our final goal was to identify markers of the oncogene-induced senescence response by comparing the expression profiles of the cell lines entering OIS after Mek activation (that is, after 4OHT treatment) with the ones bypassing this response. Keywords: other
2005-05-15 | GSE2487 | GEO
Project description:In the present study, we analyse the effect of knocking down TLR2 and TLR10 during oncogene induced senescence in IMR90 cells expressing a inducible version of oncogenic RAS (ER:RAS) in the transcriptome using Ampliseq RNA sequencig. We observed that TLR2 and TLR10 regulate the expression of many pro-inflammatory cytokines and chemokines that constitute the senescence associated secretory phenotype. There is also significant regulation of genes of the acute phase response.
2019-06-11 | GSE127116 | GEO
Project description:Senescence can be transmitted in a paracrine way from cells undergoing Oncogene Induced Senescence (OIS) to naM-CM-/ve normal cells. We define this phenomenon as M-bM-^@M-^\paracrine senescenceM-bM-^@M-^] We used microarrays to compare the trancriptome of cells undergoing paracrine senescence to the transcriptome of cells suffering OIS to unveil the common signatures defining both events and the similarities between them IMR90 cells were co-cultured with IMR90 ER:RAS undergoing OIS or IMR90-Vector control cells using 0.2 M-NM-<m pore transwell (anopore) to allow communication of soluble factors but physical separation of the two cell populations. The total mRNA of IMR90, IMR90 ER:RAS or IMR90 cells cultured in Transwells together with IMR90 vector or IMR90 ER:RAS cells during 7 days in the presence of 200 nM 4OHT and 0.5 % FBS was extracted and hybridized on Affymetrix microarrays to compare paracrine senescence to OIS.
2013-06-13 | E-GEOD-41318 | biostudies-arrayexpress
Project description:To determine the genome-wide pattern of H3K27ac in IMR90 (ATCC CCL-186) cells we performed ChIP-seq upon hormone treatment (1.5 h, 1 M dexamethasone).
2018-04-12 | E-MTAB-5355 | biostudies-arrayexpress
Project description:IMR90 cells were infected with pLNC-RAS:ER (from Jesus Gil lab) with retroviral gene transfer. Infected cells were drug selected G418. The cells were induced either with ethanol as control or with 100nM final conc 4-hydroxytamoxifen (sigma H7904) for ectopic expression of protein We used RNA-Seq to detail the global programme of gene expression in human IMR90 oncogene induced senescence
2014-11-26 | E-GEOD-52848 | biostudies-arrayexpress
Project description:Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signalling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here we show that multinucleate OIS cells originated mostly from failed mitosis. Prior to senescence, mutant RasV12 activation in primary human fibroblasts compromised mitosis, associated with abnormal expression of mitotic genes that enter M-phase. Simultaneously, RasV12 activation enhanced survival of damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional up-regulation of Mcl1 was responsible for enhanced slippage of cells with mitotic defects and subsequent cell survival. Importantly, mitotic slippage and oncogene signalling synergistically induced senescence and key senescence regulators p21 and p16. We propose that activated Ras induces transcriptional changes that predispose cells undergoing OIS to mitotic stress and multinucleation. We used RNA-seq of IMR90 cells with inducible expression of oncogenic RasV12 that were synchronised in mitosis, to characterise the nature of mitotic defects that lead to multinucleation of oncogene-induced senescent cells
2015-08-13 | E-GEOD-70668 | biostudies-arrayexpress
Project description:Cellular senescence can be transmitted to neighbouring cells in a paracrine manner through different mechanisms, including soluble factors released by senescent cells. To understand the dynamic regulation of paracrine senescence, here we investigated gene expression profiles in normal human fibroblasts (IMR90) exposed to conditioned medium generated by an inducible model of fibroblast Oncogene-Induced Senescence (IMR90-ER:RAS) at different time points after induction of senescence.
2022-04-05 | GSE139563 | GEO
Project description:Differentially regulated protein during IMR90 cell senescence
2024-06-06 | PXD052883 |
Project description:Paradoxically, oncogenes that drive cell cycle progression may also trigger pathways leading to senescence, thereby inhibiting the growth of tumorigenic cells. Along these lines, Y1 cells, which carry an amplification of Ras, become senescent after treatment with the mitogen FGF-2. To understand how FGF-2 promotes senescence, we profiled the epigenome, transcriptome, proteome, and phospho-proteome of Y1 cells stimulated with FGF-2. FGF-2 caused delayed acetylation of histone H4 and higher levels of H3K27me3. Sequencing analysis revealed decreased expression of cell cycle-related genes with concomitant loss of H3K27ac. In contrast, FGF-2 promoted the expression of p21, various cytokines, and MAPK-related genes. Nuclear envelope proteins, particularly lamin B1, displayed increased phosphorylation in response to FGF-2. Proteome analysis suggested alterations in cellular metabolism, as evident by modulated expression of enzymes involved in purine biosynthesis, tRNA aminoacylation, and the TCA cycle. Altogether, the response of Y1 cells to FGF-2 is consistent with oncogene-induced senescence. We propose that Y1 cells enter senescence due to deficient cyclin expression and high levels of p21, which may stem from DNA damage or TGFb signaling.
2021-06-16 | PXD020688 | Pride