Similar Datasets
Project description:Senescence is a stable form of cell cycle arrest that is triggered in response to various pathophysiological stimuli. The three-dimensional structure of senescent cells has been previously characterised, mostly in terms of macro-domains or changes between large heterochromatic regions. In the present body of work, using a combination of HiC and targetted Capture Hi-C, we aimed to investigate the association between gene expression and local chromatin structure in senescence, particularly focusing on enhancer-promoter (EP) interactions. We show that many EP contacts are rewired in RAS-induced Senescence compared to ‘normal’, growing cells and that these are associated with cohesin binding changes and possible loop re-organisation. The genes affected by altered chromatin interactions correspond to the two main axes of senescence gene regulation: cell cycle and inflammation. Our findings are potentially relevant during ageing and in cancers with cohesin mutations, where cell cycle and inflammation are also deregulated.
2020-10-05 | GSE135090 | GEO
Project description:Senescence is a stable form of cell cycle arrest that is triggered in response to various pathophysiological stimuli. The three-dimensional structure of senescent cells has been previously characterised, mostly in terms of macro-domains or changes between large heterochromatic regions. In the present body of work, using a combination of HiC and targetted Capture Hi-C, we aimed to investigate the association between gene expression and local chromatin structure in senescence, particularly focusing on enhancer-promoter (EP) interactions. We show that many EP contacts are rewired in RAS-induced Senescence compared to ‘normal’, growing cells and that these are associated with cohesin binding changes and possible loop re-organisation. The genes affected by altered chromatin interactions correspond to the two main axes of senescence gene regulation: cell cycle and inflammation. Our findings are potentially relevant during ageing and in cancers with cohesin mutations, where cell cycle and inflammation are also deregulated.
2020-10-05 | GSE135088 | GEO
Project description:Transcription-driven cohesin accumulation is associated with secretory phenotype of senescence
| PRJNA557421 | ENA
Project description:Transcription-driven cohesin accumulation is associated with secretory phenotype of senescence [HiC]
| PRJNA557420 | ENA
Project description:Transcription-driven cohesin accumulation is associated with secretory phenotype of senescence [ChIP-Seq]
| PRJNA557423 | ENA
Project description:We found histological evidence for increased abundance of iron accumulating cells in association with fibrotic lung, kidney, and heart diseases in mice and humans. We showed that inducing iron accumulation by intratracheal iron delivery in mice is a potent inducer of inflammation, cellular senescence, and fibrosis. The aim of this study has been to understand the single cell dynamics of iron accumulation and the mechanics that link it to in vivo senescence and to fibrogenesis. To get deeper insight into how different cell types respond to iron accumulation, we performed single nuclei RNA sequencing (snRNA-seq) of lungs from mice which received a single intratracheal dose of iron 2 or 6 days prior to analysis, or PBS 6days prior to analysis (control).
2023-08-18 | E-MTAB-13032 | biostudies-arrayexpress
Project description:The METTL3-METTL14 complex, the "writer" of N6-methyladenosine (m6A), plays an important role in many biological processes. Previous studies have shown that Mettl3 overexpression can increase the level of m6A and promote somatic cell reprogramming. Here, we demonstrate that Mettl14, another component of the methyltransferase complex, can significantly enhance the generation of induced pluripotent stem cells (iPSCs) in an m6A-independent manner. In cooperation with Oct4, Sox2, Klf4, and c-Myc, overexpressed Mettl14 transiently promoted senescence-associated secretory phenotype (SASP) gene expression in non-reprogrammed cells in the late stage of reprogramming. Subsequently, we demonstrated that interleukin-6 (IL-6), a component of the SASP, significantly enhanced somatic cell reprogramming. In contrast, blocking the SASP using a senolytic agent or a nuclear factor κB (NF-κB) inhibitor impaired the effect of Mettl14 on reprogramming. Our results highlight the m6A-independent function of Mettl14 in reprogramming and provide new insight into the interplay between senescence and reprogramming in vitro.
| S-EPMC9391510 | biostudies-literature
Project description:The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine play critical roles in protein synthesis and energy metabolism. Despite their widespread use as nutritional supplements, BCAAs' full effects on mammalian physiology remain uncertain due to the complexities of BCAA metabolic regulation. Here a novel mechanism linking intrinsic alterations in BCAA metabolism is identified to cellular senescence and the senescence-associated secretory phenotype (SASP), both of which contribute to organismal aging and inflammation-related diseases. Altered BCAA metabolism driving the SASP is mediated by robust activation of the BCAA transporters Solute Carrier Family 6 Members 14 and 15 as well as downregulation of the catabolic enzyme BCAA transaminase 1 during onset of cellular senescence, leading to highly elevated intracellular BCAA levels in senescent cells. This, in turn, activates the mammalian target of rapamycin complex 1 (mTORC1) to establish the full SASP program. Transgenic Drosophila models further indicate that orthologous BCAA regulators are involved in the induction of cellular senescence and age-related phenotypes in flies, suggesting evolutionary conservation of this metabolic pathway during aging. Finally, experimentally blocking BCAA accumulation attenuates the inflammatory response in a mouse senescence model, highlighting the therapeutic potential of modulating BCAA metabolism for the treatment of age-related and inflammatory diseases.
| S-EPMC10787106 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Oncogene-induced senescence (OIS) and therapy-induced senescence (TIS), while tumor-suppressive, also promote procarcinogenic effects by activating the DNA damage response (DDR), which in turn induces inflammation. This inflammatory response prominently includes an array of cytokines known as the senescence-associated secretory phenotype (SASP). Previous observations link the transcription-associated methyltransferase and oncoprotein MLL1 to the DDR, leading us to investigate the role of MLL1 in SASP expression. Our findings reveal direct MLL1 epigenetic control over proproliferative cell cycle genes: MLL1 inhibition represses expression of proproliferative cell cycle regulators required for DNA replication and DDR activation, thus disabling SASP expression. Strikingly, however, these effects of MLL1 inhibition on SASP gene expression do not impair OIS and, furthermore, abolish the ability of the SASP to enhance cancer cell proliferation. More broadly, MLL1 inhibition also reduces âSASP-likeâ inflammatory gene expression from cancer cells in vitro and in vivo independently of senescence. Taken together, these data demonstrate that MLL1 inhibition may be a powerful and effective strategy for inducing cancerous growth arrest through the direct epigenetic regulation of proliferation-promoting genes and the avoidance of deleterious OIS- or TIS-related tumor secretomes, which can promote both drug resistance and tumor progression. Previously published samples GSM1135046, GSM1135044, GSM1135047, and GSM1135045 were also studied in this investigation and appear in GSE36641. This did not involve re-sequencing or re-alignment, nor any other deviation from the data protocols in that series. Refer to individual Series
2016-02-22 | E-GEOD-78142 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-07-18 | GSE117210 | GEO