Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor [bulk RNA-seq]

ABSTRACT: Cellular senescence is now acknowledged as a key contributor to organismal ageing and late-life disease. Although popular, the study of senescence in vitro can be complicated by the prolonged and asynchronous timing of cells committing to it and its paracrine effects. To address these issues, we repurposed the small molecule inhibitor inflachromene (ICM) to induce senescence to human primary cells. Within six days of treatment with ICM, senescence hallmarks, including the nuclear eviction of HMGB1 and -B2, are uniformly induced across the cell population. By comparing various high throughput datasets from ICM-induced and replicative senescence, we uncovered significant similarities between the two states. Notably, ICM suppresses the proinflammatory secretome associated with senescence, thus alleviating most paracrine effects. In summary, ICM rapidly and synchronously induces a senescence-like phenotype that allows us to study its core regulatory program without any confounding heterogeneity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE238252 | GEO | 2024/04/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor [microC]

Project description:Cellular senescence is now acknowledged as a key contributor to organismal ageing and late-life disease. Although popular, the study of senescence in vitro can be complicated by the prolonged and asynchronous timing of cells committing to it and its paracrine effects. To address these issues, we repurposed the small molecule inhibitor inflachromene (ICM) to induce senescence to human primary cells. Within six days of treatment with ICM, senescence hallmarks, including the nuclear eviction of HMGB1 and -B2, are uniformly induced across the cell population. By comparing various high throughput datasets from ICM-induced and replicative senescence, we uncovered significant similarities between the two states. Notably, ICM suppresses the proinflammatory secretome associated with senescence, thus alleviating most paracrine effects. In summary, ICM rapidly and synchronously induces a senescence-like phenotype that allows us to study its core regulatory program without any confounding heterogeneity.

2024-04-24 | GSE238250 | GEO

Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor [scRNA-seq]

2024-04-24 | GSE238255 | GEO

Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor [CUT&TAG]

2024-04-24 | GSE238253 | GEO

Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor [Ribo-seq]

2024-04-24 | GSE238251 | GEO

Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor [factory RNA-seq]

2024-04-24 | GSE238254 | GEO

HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence [ChIP-seq]

Project description:Spatial organization and gene expression of mammalian chromosomes are maintained and regulated in conjunction with cell cycle progression. This is perturbed once cells enter senescence and the highly abundant HMGB1 protein is depleted from nuclei to act as an extracellular proinflammatory stimulus. Despite its physiological importance, we know little about the positioning of HMGB1 on chromatin and its nuclear roles. To address this, we mapped HMGB1 binding genome-wide in two primary cell lines. We integrated ChIP-seq and Hi-C with graph theory to uncover clustering of HMGB1-marked topological domains that harbour genes required for paracrine senescence. Using sCLIP and functional tests, we show that HMGB1 is also a bona fide RNA-binding protein (RBP) binding hundreds of mRNAs. It presents an interactome rich in RBPs implicated in senescence regulation. The mRNAs of many of these RBPs are directly bound by HMGB1 and regulate the availability of SASP-relevant transcripts. Our findings highlight a broader than hitherto assumed role for HMGB1 in coordinating chromatin folding and RNA homeostasis as part of a regulatory loop controlling cell-autonomous and paracrine senescence.

2021-04-10 | GSE171781 | GEO

HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence [Ribo-seq]

2021-04-10 | GSE171780 | GEO

HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence [RNA-seq]

2021-04-10 | GSE171779 | GEO

Proteomic analysis of the secretome from 4T1 breast cancer cells upon Stat3 silencing.

Project description:Stat3 has been acknowledged as an oncogene that has dual protumorigenic activity in a cell-intrinsic way, by promoting cancer cell proliferation and survival and in a paracrine mode, acting as suppressor of immune cell attack. We demonstrated that Stat3 silencing with a small interfering RNA (siRNA) induced a senescence program in Stat3-addicted cancer cells and leads to the production of a senescence associated secretory phenotype (SASP) that has several antitumor properties. The composition of the SASP induced by Stat3 silencing is poorly characterized. The goal of the project was to analyze the protein content in the secretome released by the mouse breast cancer cell line 4T1 after Stat3 silencing with a small interfering RNA.

2020-01-21 | PXD013948 | Pride

FBP1 loss disrupts liver metabolism and promotes tumourigenesis through a hepatic stellate cell senescence secretome

Project description:Crosstalk between deregulated hepatocyte metabolism and cells within the tumour microenvironment, and consequent effects on liver tumourigenesis, are incompletely understood. We show here that hepatocyte specific loss of the gluconeogenic enzyme fructose 1,6-bisphosphatase 1 (FBP1) disrupts liver metabolic homeostasis and promotes tumour progression. FBP1 is universally silenced in both human and murine liver tumours, and hepatocyte-specific Fbp1 deletion results in steatosis, concomitant with activation and senescence of hepatic stellate cells (HSCs), exhibiting a senescence-associated secretory phenotype (SASP). Depleting senescent HSCs by senolytic treatment with dasatinib/quercetin or ABT-263 inhibits tumour progression. We further demonstrate that FBP1-deficient hepatocytes promote HSC activation by releasing HMGB1; blocking its release with the small molecule inflachromene limits FBP1-dependent HSC activation, subsequent SASP development, and tumour progression. Collectively, these findings provide genetic evidence for FBP1 as a metabolic tumour suppressor in liver cancer and establish a critical link between hepatocyte metabolism and HSC senescence that promotes tumour growth.

2020-03-02 | MSV000085045 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data