Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chromatin reorganization drives expression of functional maturation genes in senescent pancreatic beta cells (Series2 - chromatin sccessibility, ATAC-seq)

ABSTRACT: Using a unique model of cultured human beta cell senescence we show that chromatin reorganization leads to activation of enhancers regulating functional maturation genes, concomitantly with acquisition of glucose-stimulated insulin secretion capacity. Interferon-response genes are elevated in senescent beta cells, but cytokine-encoding senescence-associated secretory phenotype (SASP) genes are not. Human beta cell senescence thus involves chromatin-driven upregulation of a functional maturation program and of interferon-stimulated genes, changes that could increase both insulin secretion and immune reactivity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE207818 | GEO | 2024/06/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Chromatin reorganization drives expression of functional maturation genes in senescent pancreatic beta cells (Series4- chromatin profiles, MINT-ChIP)

Project description:Using a unique model of cultured human beta cell senescence we show that chromatin reorganization leads to activation of enhancers regulating functional maturation genes, concomitantly with acquisition of glucose-stimulated insulin secretion capacity. Interferon-response genes are elevated in senescent beta cells, but cytokine-encoding senescence-associated secretory phenotype (SASP) genes are not. Human beta cell senescence thus involves chromatin-driven upregulation of a functional maturation program and of interferon-stimulated genes, changes that could increase both insulin secretion and immune reactivity.

2024-06-26 | GSE207825 | GEO

Chromatin reorganization drives expression of functional maturation genes in senescent pancreatic beta cells (Series3 - Chromatin profiles, ChIP-seq)

2024-06-26 | GSE207822 | GEO

Chromatin reorganization drives expression of functional maturation genes in senescent pancreatic beta cells (Series1 - Transcriptome)

2024-06-26 | GSE207816 | GEO

SC-beta Cell in vivo Maturation

Project description:Stem cell-derived β (SC-β) cells are an emerging regenerative therapy to compensate for loss of functional β cell mass in diabetes. Glucose-stimulated insulin secretion in SC-β cells is variable in vitro but stabilizes after transplantation and maturation under the kidney capsule of mice. We identified mechanisms correlated with functional maturation using RNA-sequencing and co-expression network analysis. In vivo maturation enhanced glucose-stimulated but not basal insulin secretion, up-regulated β cell hormones IAPP and ADCYAP1, increased expression of maturation markers MAFA, UCN3, and SIX2, and resolved endocrine identity of incompletely specified polyhormonal cells produced during differentiation. Transplantation promoted calcium signalling, induced exocytotic machinery supporting hormone secretion and improved stimulus-secretion coupling that fine-tunes insulin secretion. Growth hormone signalling emerged as candidate driver of in vivo maturation and was confirmed in vitro. Also, a large co-expression module correlated with HbA1c and was enriched in genes up-regulated during in vivo maturation but down-regulated in hyperglycaemic and palmitate stress conditions, suggesting that transcriptional maturation of SC-β cells in vivo mirrors processes lost in diabetic β cells.

2019-08-19 | GSE135944 | GEO

Acceleration of beta cell aging plays a key role in diabetes and senolysis improves metabolic, functional and cellular outcomes

Project description:The risk of type 2 diabetes increases with age. Although changes in function and proliferation of aged beta cells resemble those preceding the development of diabetes, the contribution of beta cell aging and senescence remains unclear. The proportion of aged beta cells increases with animal age but even in young mice, senescent beta cells can be found. We showed that different models of insulin resistance accelerated aging and senescence marker expression in beta cells, BGal, led to loss of function and impaired glucose tolerance. Clearance of p16Ink4a+ cells, using the INK-ATTAC mouse model, ameliorated glucose metabolism, insulin secretion and decreased expression of aging, senescence and SASP genes in pancreatic islets. Senolytic drug ABT263 also improved glucose metabolism and beta cell identity when administered during insulin resistance. Human beta cells from diabetic and non-diabetic donors shared some of the same biology laying the foundation for translation into humans. These novel findings lay the framework to pursue senolysis of beta cells as a preventive and alleviating strategy for T2D.

2019-05-10 | GSE121539 | GEO

Unique human beta-cell senescence-associated secretory phenotype (SASP) reveal conserved signaling pathways and heterogeneous factors

Project description:The aging of pancreatic beta-cells may undermine their ability to compensate for insulin resistance, leading to the development of type 2 diabetes (T2D). Aging beta-cells acquire markers of cellular senescence and develop a senescence-associated secretory phenotype (SASP) that can lead to senescence and dysfunction of neighboring cells through paracrine actions, contributing to beta-cell failure. Herein, we defined the beta-cell SASP signature based on unbiased proteomic analysis of conditioned media of cells obtained from human senescent beta-cells. These experiments revealed that the beta-cell SASP is enriched for factors associated with inflammation, cellular stress response, and extracellular matrix remodeling across species.

2021-03-18 | GSE162521 | GEO

Identification of Scrt1, a new transcriptional regulator of beta-cell maturation using chromatin accessibility variations

Project description:Pancreatic beta-cells are highly specialized cells that produce and release insulin in response to nutrients, hormones and neurotransmitters. Glucose-induced insulin secretion, a unique feature of fully differentiated beta-cells, is only acquired after birth and is preceded by a phase of intense beta-cell proliferation. These events occurring in the neonatal period are critical for the establishment of an appropriate functional beta-cell mass covering the insulin needs throughout life. However, key regulators of gene expression and cis-regulatory elements involved in the cellular reprogramming along maturation remain to be elucidated. This project addresses this issue by using ATAC-seq (Assay for Transposase-Accessible Chromatin with high throughput sequencing) permitting a fine genome-wide mapping of chromatin accessibility. This approach is used to compare open chromatin regions in newborn and adult rat beta-cells. We obtained a genome-wide picture of chromatin accessible sites (100000) among which 20% were differentially accessible during maturation. Nearly 60% of these sites were in the proximity of significantly differentially expressed genes. An analysis of transcription factor binding sites revealed key known and unforeseen transcription factors which could explain these changes. We validated a transcriptional repressor named SCRT1, that depicted a significant effect on beta-cell proliferation and targeted several genes implicated in the acquisition of glucose-stimulated insulin secretion function. Thus, we were able to find several known and unforeseen key transcriptional regulators acting at cis-regulatory sites and promoters which depicted a differential accessibility and induced differential gene expression along maturation. These findings could be of interest to induce maturation of surrogate insulin-producing cells.

2020-05-01 | GSE130651 | GEO

Pleiotrophic function of BAFF to promote a senescence-associated secretome and growth arrest

Project description:Senescent cells release a variety of cytokines, proteases and growth factors collectively defined as the Senescent Secretory Associated Phenotype (SASP). Sustained SASP induces a pattern of chronic inflammation associated with aging and implicated in multiple age-related diseases. Here, we investigated the expression and function of the immunomodulatory cytokine BAFF (B-cell activating factor), a SASP factor, in multiple senescence models. First, we characterized BAFF production across different senescence models, including senescent human diploid fibroblasts (WI-38, IMR-90) and monocytic leukemia cells (THP-1), and tissues of mice induced to undergo senescence. We identified IRF1 (interferon response factor 1) as a transcription factor required for promoting BAFF mRNA transcription in senescence, and found that suppressing BAFF production decreased the senescent phenotype in both monocytes and fibroblasts. Importantly, the influence of BAFF on the senescence program was cell type-specific: in monocytes, BAFF promoted the early activation of NF-κB and general SASP secretion, while in fibroblasts, BAFF contributed to the production and function of TP53 (p53). Overall, BAFF silencing affected shared senescence-associated phenotypes including IL6 secretion, SA-beta-Gal staining, and γ-H2AX accumulation. We propose that BAFF is a novel biomarker of senescence and a potential target for senotherapy.

2023-04-07 | GSE213993 | GEO

Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence

Project description:Cellular senescence is triggered by various distinct stresses and characterized by a permanent cell cycle arrest. Senescent cells secrete a variety of inflammatory factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The mechanism(s) underlying the regulation of the SASP remains incompletely understood. Here we define a role for innate DNA sensing in the regulation of senescence and the SASP. We find that cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments (CCFs) in senescent cells. The activation of cGAS, in turn triggers the production of SASP factors via Stimulator of interferon genes (STING), thereby promoting paracrine senescence. We demonstrate that diverse stimuli of cellular senescence engage the cGAS-STING pathway in vitro and we show cGAS-dependent regulation of senescence upon irradiation and oncogene activation in vivo. Our findings provide insights into the mechanisms underlying cellular senescence by establishing the cGAS-STING pathway as a crucial regulator of senescence and the SASP.

2017-06-20 | GSE100102 | GEO

TEAD4 delays cellular senescence by remodeling chromatin accessibility at H3K27ac-occupied enhancer regions [CUT&Tag]

Project description:Dramatic alterations in epigenetic landscapes are known to affect genome accessibility and their transcriptional program. Extensive evidences have emerged that senescent cells accumulate profound chromatin tremendous reordering upon senescence entry, yet, the underlying mechanisms between epigenetic parameters and gene expression profile have not been fully clarified. In this report, we delineate the genome-wide redistribution of accessible chromatin regions leading to broad transcriptome effects during UC-MSCs senescence. We report the distinct senescence-activated accessibility regions (SAAs) are always distributed in H3K27ac decorated enhancer regions, where the SAAs are responsible for elevated flanking SASP expression and aberrant cellular signaling relevant to SASP secretion. Mechanistically, a single transcription factor, TEAD4, shifting away from H3K27ac-labled SAAs and leading to prominent chromatin accessibility reconstruction during senescence. The enhanced signal of SAAs driven by TEAD4 suppression subsequently induce a robust decrease of adjacent SASP genes expression and downstream factors secretion, and finally, contributing to the progression of senescence. Our findings illustrate a dynamic landscape of chromatin accessibility following senescence entry and reveal an insightful function for TEAD4 in regulating the broad chromatin state that modulate the overall transcriptional program of the SASP genes.

2023-04-01 | GSE226294 | GEO

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