Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transient ER stress cell-autonomously promotes beta cell cycling

ABSTRACT: Regenerating endogenous pancreatic ß-cells is a potentially curative yet currently elusive strategy for diabetes therapy. Mimicking the microenvironment of the developing pancreas and leveraging vascular signals that support pancreatic endocrinogenesis may promote ß-cell regeneration. We aimed to investigate whether recovery from experimental hypovascularization of the endocrine pancreas, achieved by modulating the transgenic production of a VEGF-A blocker in ß-cells, could trigger mouse ß-cell proliferation. Serendipitously, we found that transgene overexpression in ß-cells induces endoplasmic reticulum (ER) stress and that subsequent relief from this stress stimulates ß-cell proliferation independent of vessel recovery. Transient GFP overexpression in vivo and transient chemical induction of ER stress in vitro replicated this ß-cell cycling response. Our findings highlight the potential side effects of ER stress due to transgene overexpression in ß-cells and assert that ER stress relief serves as a potent regenerative stimulus.

ORGANISM(S): Mus musculus

PROVIDER: GSE274443 | GEO | 2025/12/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A unique ISR Program Determines Cellular Responses to Chronic Stress

Project description:Integrated Stress Response (ISR) is a homeostatic mechanism induced by endoplasmic reticulum (ER) stress. With acute/transient ER stress, decreased global protein synthesis and increased uORF mRNA translation are followed by translation normalization. Here, we report a dramatically different response during more physiologically relevant chronic ER stress. This unique ISR program is characterized by persistently elevated uORF mRNA translation and concurrent gene expression reprogramming, which permits simultaneous stress sensing and proteostasis. PERK-dependent switching from eIF4F/eIF2B- to eIF3D/GADD34-regulated translation initiation results in partial but not complete translation recovery, and together with transcriptional reprogramming, selectively bolsters expression of proteins with ER functions. Coordination of these transcriptional and translational changes prevents ER dysfunction and inhibits “foamy cell” development, thus establishing a molecular basis for understanding human diseases associated with ER dysfunction.

2018-01-05 | GSE90070 | GEO

Elevated HuR in Pancreas Promotes a pancreatitis-like Inflammatory Microenvironment that Facilitates Tumor Development

Project description:Gene expression in pancreas of 6 month-old C mice bearing Pdx1/Cre transgene having normal pancreas was compared to that of pancreas of 6 week old TC mice in which HuR protein was specifically overexpressed in the pancreas. We used microarrays to identify gene expression changes associated with HuR overexpression-induced fibro-inflammatory response in the pancreas.

2017-11-27 | GSE102508 | GEO

Alterations in the nascent proteome during translation attenuation in response to mitochondrial stress induced by carbonyl cyanide m-chlorophenyl hydrazine (CCCP) and in response to EEF1A1 knockdown

Project description:This submission is a part of a proteomic resource consisting of four independent datasets and their meta-analysis which describe: the detailed landscape of changes in the nascent proteome at high temporal resolution with 30 min intervals upon rapid and reversible global translation attenuation in response to transient mitochondrial membrane depolarization and during the subsequent recovery of physiological translation upon the relief of this stress (PXD043942), comparison of nascent proteome alterations in response to two types of challenge to protein homeostasis – proteasome inhibition and mitochondrial inner membrane depolarization (this submission, datasets expII and expIV) and finally nascent proteome alterations happening after silencing of elongation factor EEF1A1 in untreated and stress conditions (this submission, dataset expIII).

2024-10-02 | PXD054502 | Pride

A common CTRB misfolding variant associated with pancreatic cancer risk causes ER stress and inflammation in mice

Project description:Objective: Genome wide association studies have identified an exon 6 CTRB2 deletion variant that is associated with increased PDAC risk. To acquire evidence on its causal role, we developed a new mouse strain carrying an equivalent variant in Ctrb1, the mouse orthologue of CTRB2. Design: We used CRISPR/Cas9 to introduce a 707bp deletion in Ctrb1 encompassing exon 6 (Ctrb1Dexon6). This mutation closely mimics the human deletion variant. Mice carrying the mutant allele were extensively profiled at 3 months to assess their phenotype. Results: Ctrb1Dexon6 mutant mice express a truncated CTRB1 that accumulates in the ER. The pancreas of homozygous mutant mice displays reduced chymotrypsin activity and total protein synthesis. The histological aspect of the pancreas is inconspicuous but ultrastructural analysis shows evidence of dramatic ER stress, and cytoplasmic and nuclear inclusions. Transcriptomic analyses of the pancreas of mutant mice reveals acinar program down-regulation and increased activity of ER stress-related and inflammatory pathways. Heterozygous mice have an intermediate phenotype. Agr2 is one of the most up-regulated genes in mutant pancreata. Ctrb1Dexon6 mice exhibit impaired recovery from acute caerulein-induced pancreatitis. Administration of TUDCA or sulindac partially alleviates the phenotype. A transcriptomic signature derived from the mutant pancreata is significantly enriched in normal human pancreas of CTRB2 exon 6 deletion variant carriers from the GTEx cohort. Conclusions: This mouse strain provides formal evidence that the exon 6 deletion variant causes ER stress and inflammation in vivo, providing an excellent model to understand its contribution to pancreatic ductal adenocarcinoma and to identify preventive strategies.

2024-07-26 | GSE272278 | GEO

Transient ER stress cell-autonomously promotes beta cell cycling

Project description:Transient ER stress cell-autonomously promotes beta cell cycling

| PRJNA1146436 | ENA

A conserved AAA+ ATPase network regulates endoplasmic reticulum stress-induced transcription

Project description:In C. elegans cdc-48.2(-/-) mutant animals, ER stress-mediated expression of the UPR ckb-2::GFP reporter transgene is abolished. Here, we have used this phenotype in a genome-wide RNAi screen to identify genes involved in the CDC-48.2 mediated ER stress transcription. Combined with a comparative proteomic analysis, this approach has allowed us to identify the AAA+ ATPase RUVB-2 as a novel regulator of the ER stress response and a CDC-48 degradation target.

2015-09-30 | PXD000636 | Pride

Alternation of gene expression when expressing FASN-CTF in ced-3(-) null animalsn under ER stress

Project description:To investigate how FASN-CTF affect gene expression under ER stress, we expressed auxin-induced-degron (AID) controlled FASN-CTF transgene in ced-3(-) animals which had elevated stress response.

2023-05-09 | GSE226048 | GEO

RNA sequencing analysis shows that titanium dioxide nanoparticles induce endoplasmic reticulum stress, which has a central role in mediating plasma glucose in mice

Project description:Titanium dioxide nanoparticles (TiO2 NPs) constitute the top five NPs in use today. A recent study determined that oral administration of TiO2 NPs increases plasma glucose in mice. In the current study, RNA sequencing (RNA-seq) technology was used to investigate genome-wide effects of TiO2 NPs. Clustering analysis of the RNA-seq data showed the most significantly enriched gene ontology terms and KEGG pathways related to the endoplasmic reticulum (ER) and ER stress. Molecular biology verification showed that TiO2 NPs activated a xenobiotic biodegradation response and increased expression of cytochrome P450 family genes in mouse livers, thus inducing ER stress in mice. ER stress activated MAPK and NF-B pathways and induced an inflammation response, resulting in phosphorylation of the insulin receptor substrate 1 and, consequently, insulin resistance. This was the main mechanism by which TiO2 NPs increased plasma glucose in mice. Meanwhile, ER stress disturbed the monooxygenase system, and thus generated reactive oxygen species (ROS). Relief of ER stress with 4-phenylbutyric acid inhibited all the above effects of TiO2 NPs, including the generation of ROS. Therefore, TiO2 NP-induced ER stress was a decisive factor with a central role in plasma glucose disturbance in mice.

2019-11-14 | GSE107084 | GEO

Functional characterization of thousands of type 2 diabetes-associated and chromatin-modulating variants under steady state and endoplasmic reticulum stress

Project description:We tested >13,000 sequences containing each allele of 6,628 SNPs associated with altered in vivo chromatin accessibility in human islets and/or type 2 diabetes risk (T2D GWAS SNPs) for transcriptional activity in ß cell under steady state and endoplasmic reticulum (ER) stress conditions using the massively parallel reporter assay (MPRA).

2020-02-21 | GSE145643 | GEO

ena-DATASET-JAX-12-06-2021-17:12:30:945-849 - samples

Project description:This dataset includes 60 BAM files from HF2354, HF3016 glioblastoma cell lines subjected to continuous stress (hypoxia, 3-day and 9-day), stress followed by recovery (irradiation, 4-day stress exposure and 5-day recovery), and no stress/normoxia controls and profiled using reduced-representation bisulfite sequencing.

| EGAD00001007770 | EGA

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