Bulk RNA-seq of HFF cell senescence model induced by oncogene activation
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PROVIDER: PRJNA1188032 | ENA |
REPOSITORIES: ENA
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Project description:To investiage the mechanism of cellular senescence, we established a model of oncogene RAS-induced cellular senescence in human foreskin fibroblasts (HFF cells). We transduced an estrogen receptor fused to the H-RASG12V protein (ER:RAS) in HFF, which can be induced by 4-hydroxytamoxifen (4-OHT).
2025-03-05 | GSE282274 | GEO
Project description:Sequencing of human HFF fibroblasts during replicative senescence (smallRNA)
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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:Oncogene inactivation induced senescence facilitates tumor relapse
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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.
2017-03-30 | GSE86546 | GEO
Project description:We generated a humanized mouse model of oncogene-induced senescence in hematopoietic stem and progenitor cells by expressing the activated oncogene BRAF-V600E. Mice succumbed to bone marrow failure and multi-organ dissemination of aberrant macrophages and dendritic cells. We observed a myeloid-restricted hematopoiesis,and uncovered the activation of a senescence program, characterized by growth arrest and senescence-associated secretory phenotype (SASP), which involved also non-mutated bystander cells.
2021-05-14 | GSE144058 | GEO
Project description:small RNA gene expression profiles of senescent human fibroblasts were compared to young proliferating fibroblasts. RNA-seq data comprises 5 groups: 16, 26, 46, 64 and 74 population doublings of HFF fibroblasts. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
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Project description:DNMT1 drives 4D genome rewiring during oncogene induced senescence
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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:While, transcriptional and epigenetic changes associated senescence processes are well studied, the 3D chromatin changes associated with it remains elusive. In this study, we have generated genome wide chromatin interaction maps (Hi-C), epigenetic (ChIP-Seq), replication-timing and gene expression (RNA-Seq) profiles from replication induced (RS) and oncogene induced (OIS) senescent cells. As senescence associated heterochromatin foci (SAHFs) differentiates both RS and OIS nuclei, we identified the regions that constitute SAHFs and called them Senescence Associated Heterochromatin Domains (SAHDs). Further, screening of candidate factors for SAHF induction allowed us to identify DNMT1 as a novel component that induces SAHFs by stimulation of HMGA2 expression. DNMT1 depletion does not reverse the senescence process, however, instead, depleted cells transition to a 3D genome conformation akin to that of cells in replicative senescence, suggesting that acute senescence induction (OIS) involves SAHF formation in addition to the RS-dependent 3D genome rewiring.
2020-03-27 | GSE130306 | GEO