Gene expression analysis of cells undegoing oncogene induced senescence upon knockdown or ARID1B
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE75207 | GEO | 2016/11/12
SECONDARY ACCESSION(S): PRJNA302803
REPOSITORIES: GEO
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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:We transduced either an empty vector or ARID1B cDNA in IMR90 cells. Cells were selected with puromycin and 6 days after the infection we collected the RNA. ARID1B is a member of the SWI/SNF chromatin-remodeling complex. Our previous experiments showed that knockdown of ARID1B allows cells to bypass cellular senescence. By performing RNA-seq we have shown that ARID1B expression can induce a set of genes involved in the senescence response.
2016-11-12 | GSE75291 | GEO
Project description:IMR90 ER:RAS cells were infected with 2 different lentiviral pGIPZ shRNAs against AHCY or with an empty vector (EV). We treated IMR90 ER:RAS cells with 4OHT to induce RAS activation or with vehicle (DMSO) as a non-senescent control. RNA was collected 6 days after the start of the experiment once the senescence program has been fully implemented. Our previous experiments showed that knockdown of AHCY prevents senescence. By performing RNAseq, we have unveiled that AHCY knockdown prevents upregulation of a set of genes essential for the onset of senescence and its associated secretory phenotype.
2022-07-19 | GSE155904 | 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 examine effects of COPI depletion on senescence transcriptional signatures we generated cell lines (IMR90 or IMR90 ER:RAS cells) with inducible 2 COPI shRNAs or control shRNAs and induced to senesce with either treatment with Bleomycin or 4OHT treatment. Transcriptional analysis was performed 3 days after induction of doxycycline inducible harpins and 10 days after senescence induction.
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Project description:We depleted XPO7 by shRNA in IMR90 ER:RAS cells. 5 days after RAS induction by treatment with 4OHT we collected RNA. XPO7 depletion alleviates senescence induction.
2021-02-12 | GSE153921 | 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:ER:RAS-G12V expressing IMR90 cells were transduced with N1ICD-containing or control vectors before treatment with either 100nM 4-OHT or vehicle for 6 days leading to Notch-induced senescence (NIS), RAS-induced senescence (RIS) or combined Notch and Ras-induced senescence (RNIS).
2016-06-22 | GSE72404 | GEO
Project description:The expansion of repressive epigenetic marks has been implicated in heterochromatin formation during embryonic development, but the general applicability of this mechanism is unclear. Here we show that nuclear rearrangement of repressive histone marks H3K9me3 and H3K27me3 into non-overlapping structural layers characterizes senescence-associated heterochromatic foci (SAHF) formation in human fibroblasts. However, the global landscape of these repressive marks remains unchanged upon SAHF formation, suggesting that in somatic cells heterochromatin can be formed through the spatial repositioning of pre-existing repressively marked histones. This model is reinforced by the correlation of pre-senescent replication timing with both the subsequent layered structure of SAHFs and the global landscape of the repressive marks, allowing us to integrate microscopic and genomic information. Furthermore, modulation of SAHF structure does not affect the occupancy of these repressive marks nor vice versa. These experiments reveal that high-order heterochromatin formation and epigenetic remodeling of the genome can be discrete events. ChIP-seq for different histone marks in both growing and Ras-induced senescent fibroblasts, in the presence or absence of certain sh-RNAs K9me3Grow2.bed (growing) Chip Seq Analysis of H3K9me3 in ER:Ras expressing IMR90 human diploid fibroblasts d6 4OHT K9me3Sen2.bed (senescent) Chip Seq Analysis of H3K9me3 in ER:Ras expressing IMR90 human diploid fibroblasts with no treatment K9me2Grow3.bed (growing) Chip Seq Analysis of H3K9me2 in ER:Ras expressing IMR90 human diploid fibroblasts with no treatment K9me2Sen3.bed (senescent) Chip Seq Analysis of H3K9me2 in ER:Ras expressing IMR90 human diploid fibroblasts d6 4OHT K27me3Sen3.bed (senescent) Chip Seq Analysis of H3K27me3 in ER:Ras expressing IMR90 human diploid fibroblasts d6 4OHT K27me3Grow2.bed (growing) Chip Seq Analysis of H3K27me3 in ER:Ras expressing IMR90 human diploid fibroblasts with no treatment K36me3Grow2.bed (growing) Chip Seq Analysis of H3K36me3 in ER:Ras expressing IMR90 human diploid fibroblasts with no treatment K36me3Sen2.bed (senescent) Chip Seq Analysis of H3K36me3 in ER:Ras expressing IMR90 human diploid fibroblasts d6 4OHT K4me3Grow2.bed (growing) Chip Seq Analysis of H3K4me3 in ER:Ras expressing IMR90 human diploid fibroblasts with no treatment K4me3Sen3.bed (senescent) Chip Seq Analysis of H3K4me3 in ER:Ras expressing IMR90 human diploid fibroblasts d6 4OHT
2012-07-09 | E-GEOD-38442 | biostudies-arrayexpress
Project description:ER:RAS-G12V expressing IMR90 cells were treated with either 100nM 4-OHT for 6 days or 100uM Etoposide for 2 days, followed by further culture for 5 days, leading to RAS-induced senescence (RIS) and DNA-damage induced senescence (DDIS) respectively.
2016-06-22 | GSE72407 | GEO