E-GEOD-60340
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA258058
PROVIDER: E-GEOD-60340 | ExpressionAtlas | 2025-01-24
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-GEOD-60340-analysis-methods.tsv | Tabular | |||
| E-GEOD-60340-analytics.tsv | Tabular | |||
| E-GEOD-60340-analytics.tsv.undecorated | Tabular | |||
| E-GEOD-60340-analytics.tsv.undecorated.unrounded | Tabular | |||
| E-GEOD-60340-analytics.tsv.unrounded | Tabular |
Items per page: 5 1 - 5 of 141 |
Similar Datasets
Project description:Pathway Profiling of Replicative and Induced Senescence
| PRJNA258058 | ENA
Project description:Cellular senescence is a key cell-fate program that leads to an essentially irreversible proliferative arrest in potentially damaged cells. Cytokine production and signaling play a significant role in senescence. Tumor necrosis factor-alpha (TNFα), an important pro-inflammatory cytokine secreted by some senescent cells, can induce senescence in mouse and human cells. However, downstream signaling pathways and key regulatory genes linking inflammation to senescence are not fully characterized. Using human umbilical vein endothelial cells (HUVECs) as a model, we show TNFα induces permanent growth arrest and increased senescence markers such as p21, p16, and senescence-associated β-galactosidase (SA-β-gal), accompanied by persistent DNA damage and ROS. By gene expression profiling and pathway analysis, we identify the crucial involvement of inflammatory networks, an interferon signature, and persistent activation of the Janus kinase (JAK) /signal transducer and activator of transcription (STAT) pathway in TNFα-mediated senescence. TNFα initiates a STAT-dependent autocrine loop leading to sustained inflammation, DNA damage, and expression of interferon response genes to lock cells into senescence. Further, we show STAT1/3 activation is necessary for cytokine and ROS production during TNFα-induced senescence. However, inhibition of STAT1/3 did not rescue cells from TNFα-mediated senescence. Rather, blockade of STAT activation accelerated senescence, suppressed genes that control the cell cycle, and modulated TNFα-induced senescence. Our findings suggest a positive feedback mechanism via a STAT pathway that sustains cytokine production and reveal a reciprocal regulatory role of JAK/STAT in TNFα-mediated senescence.
2017-03-10 | GSE92655 | GEO
Project description:Cellular senescence is a stable proliferation arrest associated with an altered secretory pathway, the Senescence-Associated Secretory Phenotype (SASP). However, cellular senescence is initiated by diverse molecular triggers, such as activated oncogenes and shortened telomeres, and is associated with varied and complex physiological endpoints, such as tumor suppression and tissue aging. The extent to which distinct triggers activate divergent modes of senescence that might be associated with different physiological endpoints is largely unknown. To begin to address this, we performed gene expression profiling to compare the senescence programs associated with two different modes of senescence, oncogene-induced senescence (OIS) and replicative senescence (RS [in part caused by shortened telomeres]). While both OIS and RS are associated with many common changes in gene expression compared to control proliferating cells, they also exhibit substantial differences. These results are discussed in light of potential physiological consequences, tumor suppression and aging. We used microarrays to detail the global programme of gene expression after oncogene induced senescence.
2014-02-28 | E-GEOD-54402 | biostudies-arrayexpress
Project description:Although CD4 T cell senescence plays an important role in immunosenescence, the mechanisms remain unclear. We found that T cell-specific Menin deficiency results in the premature senescence of CD4 T cells, accompanied by the senescence-associated secretory phenotype (SASP) after antigenic stimulation. TH1 and TH2 differentiation was dysregulated in Menin-knockout CD4 T cells. Bach2, which regulates SASP and TH differentiation, was identified as a Menin target. Menin binds to the Bach2 locus, and controls its expression through maintenance of histone acetylation. These findings reveal a critical role of the Menin-Bach2 pathway in regulating CD4 T cell senescence and homeostasis, thus indicating the involvement of this pathway in the inhibition of age-associated development of inflammatory diseases, which are induced by immunosenescence. Examination of transcriptional factor Menin binding and histone modefications in Menin WT and KO CD4 T cells
2014-03-27 | E-GEOD-53831 | biostudies-arrayexpress
Project description:DallePazze2014 - Cellular senescene-induced
mitochondrial dysfunction
This model is described in the article:
Dynamic modelling of
pathways to cellular senescence reveals strategies for targeted
interventions.
Dalle Pezze P, Nelson G, Otten EG,
Korolchuk VI, Kirkwood TB, von Zglinicki T, Shanley DP.
PLoS Comput. Biol. 2014 Aug; 10(8):
e1003728
Abstract:
Cellular senescence, a state of irreversible cell cycle
arrest, is thought to help protect an organism from cancer, yet
also contributes to ageing. The changes which occur in
senescence are controlled by networks of multiple signalling
and feedback pathways at the cellular level, and the interplay
between these is difficult to predict and understand. To
unravel the intrinsic challenges of understanding such a highly
networked system, we have taken a systems biology approach to
cellular senescence. We report a detailed analysis of
senescence signalling via DNA damage, insulin-TOR, FoxO3a
transcription factors, oxidative stress response, mitochondrial
regulation and mitophagy. We show in silico and in vitro that
inhibition of reactive oxygen species can prevent loss of
mitochondrial membrane potential, whilst inhibition of mTOR
shows a partial rescue of mitochondrial mass changes during
establishment of senescence. Dual inhibition of ROS and mTOR in
vitro confirmed computational model predictions that it was
possible to further reduce senescence-induced mitochondrial
dysfunction and DNA double-strand breaks. However, these
interventions were unable to abrogate the senescence-induced
mitochondrial dysfunction completely, and we identified
decreased mitochondrial fission as the potential driving force
for increased mitochondrial mass via prevention of mitophagy.
Dynamic sensitivity analysis of the model showed the network
stabilised at a new late state of cellular senescence. This was
characterised by poor network sensitivity, high signalling
noise, low cellular energy, high inflammation and permanent
cell cycle arrest suggesting an unsatisfactory outcome for
treatments aiming to delay or reverse cellular senescence at
late time points. Combinatorial targeted interventions are
therefore possible for intervening in the cellular pathway to
senescence, but in the cases identified here, are only capable
of delaying senescence onset.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000582.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000582 | BioModels
Project description:To identify differentially expressed genes during cellular senescence, we performed transcriptional profiling with RNA sequencing (RNA-seq) before and after senescence induction using a stress-induced senescence model (bleomycin-induced senescence).
2021-03-17 | GSE168994 | GEO
Project description:Phenotypically, there is a heterogeneous response of cancer cells to chemotherapy or targeted therapy. While therapeutically much attention is focused on cell death, there is growing evidence suggesting that a subpopulation of cancer cells undergo therapy-induced senescence. Depending on the therapy, dose and timing, senescence may be a dominant phenotype over cell death. An integrated FACS approach identified two types of therapy-induced senescence in human melanoma cells, irreversible senescence induced by Aurora kinase inhibition vs. transient senescence induced by B-RAF kinase inhibition. Autophagy and ER stress response precede and are required for therapy-induced senescence in cancer cells, mirroring their functions in normal cells undergoing oncogene-induced senescence. Importantly, autophagy serves a survival pathway for senescent cancer cells. Antagonizing autophagy converts therapy-induced senescence into cell death but paradoxically promotes cell proliferation or quiescence. Our work calls for a rationale-based design of combination therapy for cancer treatment that should lead to a greater synergy. There are three or four replicates per treatment per time point.
2015-06-05 | E-GEOD-38466 | biostudies-arrayexpress
Project description:Phenotypically, there is a heterogeneous response of cancer cells to chemotherapy or targeted therapy. While therapeutically much attention is focused on cell death, there is growing evidence suggesting that a subpopulation of cancer cells undergo therapy-induced senescence. Depending on the therapy, dose and timing, senescence may be a dominant phenotype over cell death. An integrated FACS approach identified two types of therapy-induced senescence in human melanoma cells, irreversible senescence induced by Aurora kinase inhibition vs. transient senescence induced by B-RAF kinase inhibition. Autophagy and ER stress response precede and are required for therapy-induced senescence in cancer cells, mirroring their functions in normal cells undergoing oncogene-induced senescence. Importantly, autophagy serves a survival pathway for senescent cancer cells. Antagonizing autophagy converts therapy-induced senescence into cell death but paradoxically promotes cell proliferation or quiescence. Our work calls for a rationale-based design of combination therapy for cancer treatment that should lead to a greater synergy. There are three or four replicates per treatment per time point.
2016-09-01 | E-GEOD-50474 | biostudies-arrayexpress
Project description:We have generated ABCA1 knockout cells using CRISPR/Cas9 system and expanded single cell clones for gene expression profiling. To identify differentially expressed genes during cellular senescence in wild-type and ABCA1 knockout cells, we performed transcriptional profiling with RNA sequencing (RNA-seq) before and after senescence induction using a stress-induced senescence model (bleomycin-induced senescence).
2023-01-15 | GSE222676 | GEO
Project description:Here, through single-cell transcriptional profiling of genetically homogenous clonal cell lines, we analyzed subpopulations in all three major forms of senescence, namely Oncogene Induced Senescence (OIS), Replicative Senescence (RS), and DNA Damage Induced Senescence (DDIS).
2023-05-04 | GSE173879 | GEO