Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Integrated analyses of histone methylation and RNA expression in beta cells sorted from mice with multiparity-induced diabetes identified effector genes of pancreatic beta cell dedifferentiation and dysfunction.

ABSTRACT: Integrated analyses of histone methylation and RNA expression in beta cells sorted from mice with multiparity-induced diabetes identified effector genes of pancreatic beta cell dedifferentiation and dysfunction.

PROVIDER: PRJNA542261 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR9040230.fastq.gz	Fastqsanger.gz
	SRR9040240_1.fastq.gz	Fastqsanger.gz
	SRR9040240_2.fastq.gz	Fastqsanger.gz
	SRR9040231.fastq.gz	Fastqsanger.gz
	SRR9040241_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 24

Similar Datasets

The Anna Karenina model of β cell maturation in development and their dedifferentiation in type 1 and type 2 diabetes

Project description:Loss of mature β cell function and identity, or β cell dedifferentiation, is seen in all types of diabetes mellitus. Two competing models explain β cell dedifferentiation in diabetes. In the first model, β cells dedifferentiate in the reverse order of their developmental ontogeny. This model predicts that dedifferentiated β cells resemble β cell progenitors. In the second model, β cell dedifferentiation depends on the type of diabetogenic stress. This model, which we call the “Anna Karenina” model, predicts that in each type of diabetes, β cells dedifferentiate in their own way, depending on how their mature identity is disrupted by any particular diabetogenic stress. We directly tested the two models using a β cell-specific lineage-tracing system coupled with RNA-sequencing in mice. We constructed a multidimensional map of β cell transcriptional trajectories during the normal course of β cell postnatal development, and during their dedifferentiation in models of both type 1 diabetes (NOD) and type 2 diabetes (BTBR-Lepob/ob). Using this unbiased approach, we show here that despite some similarities between immature and dedifferentiated β cells, β cells dedifferentiation in the two mouse models is not a reversal of developmental ontogeny and is different between different types of diabetes.

2021-03-12 | GSE168743 | GEO

The Polycomb-dependent epigenome controls β-cell dysfunction, dedifferentiation and diabetes

Project description:To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single cell transcriptomics to mine for evidence of chromatin dysregulation in type-2 diabetes. We find two chromatin-state signatures that track β-cell dysfunction in mice and humans: ectopic activation of bivalent Polycomb-silenced domains and loss of expression at an epigenomically unique class of lineage-defining genes. β-cell specific Polycomb (Eed/PRC2) loss of function in mice triggers diabetes-mimicking transcriptional signatures and highly penetrant, hyperglycemia-independent, dedifferentiation, indicating that PRC2 dysregulation contributes to disease. The work provides novel resources for exploring β-cell transcriptional regulation and identifies PRC2 as necessary for long-term maintenance of β-cell identity. Importantly, the data suggest a two-hit (chromatin and hyperglycemia) model for loss of β-cell identity in diabetes.

2018-02-26 | GSE110648 | GEO

RNA Seq analysis of pancreatic beta cell transcriptome during dedifferentiation

Project description:We report RNA Seq analysis using Illumina nextSeq500 of human beta cells EndoC-BH1 treated with FGF2 to induce dedifferentiation. FGF2 treatment induced dedifferentiation of EndoC-BH1 cells. Indeed, we observed a strong decrease in expression of β-cell markers, (INS, MAFB, SLC2A2, SLC30A8 and GCK). Opposingly, we identifed positive markers of human β cell dedifferentiation, as attested by increased expression of mature β-cell disallowed transcription factors (MYC, HES1, SOX9 and NEUROG3). Interestingly, our temporal analysis revealed that loss of expression of β cell specific markers preceded the induction of β cell disallowed genes.

2018-02-26 | GSE103383 | GEO

Klf6 protects β-cells against insulin resistance-induced dedifferentiation

Project description:In the pathogenesis of type 2 diabetes development of insulin resistance triggers an increase in pancreatic β-cell insulin secretion capacity and β-cell number. Failure of this compensatory mechanism is caused by a dedifferentiation of β-cells, which leads to insufficient insulin secretion and diabetic hyperglycemia. The β-cell factors that normally protect against dedifferentiation remain poorly defined. Here, through a systems biology approach, we identify the transcription factor Klf6 as a regulator of β-cell adaptation to metabolic stress. We show that inactivation of Klf6 in mouse β-cells blunts their proliferation induced by the insulin resistance of pregnancy, high-fat high-sucrose feeding, and insulin receptor antagonism. Transcriptomic analysis showed that Klf6 controls the expression of β-cell proliferation genes and, in the presence of insulin resistance, it prevents the down-expression of genes controlling mature β-cell identity and the induction of disallowed genes that impair insulin secretion; its expression also limits the transdifferentiation of β-cells into alpha cells. Our study identifies a new transcription factor that protects β-cells against dedifferentiation and which may be targeted to prevent diabetes development.

2020-03-01 | GSE137187 | GEO

The Polycomb-dependent epigenome controls β-cell dysfunction, dedifferentiation and diabetes

Project description:The Polycomb-dependent epigenome controls β-cell dysfunction, dedifferentiation and diabetes

| PRJNA434190 | ENA

Stress-induced beta cell dedifferentiation prior to immune cell infiltration prevents type 1 diabetes [Single]

Project description:Immune-mediated destruction of insulin-producing β-cells causes type 1 diabetes (T1D). However, how β-cells themselves participate in the disease process is poorly understood. Here, we report that modulating the unfolded protein response (UPR) in β-cells of non-obese diabetic (NOD) mice in early stages of disease results in preserved β-cell function, substantially reduced islet immune cell infiltration, and β-cell apoptosis leading to protection from T1D. NOD mice that lack the UPR sensor IRE1α in β-cells show greatly reduced expression of β-cell identity markers, islet autoantigens, and genes involved in antigen presentation. These mice exhibit upregulation of immune inhibitory markers in β-cells and significantly less cytotoxic CD8+ T cells in the pancreas. Our results indicate that triggering transient β-cell dedifferentiation via targeting a specific branch of the UPR in β-cells, prior to insulitis, allow β-cells to escape from immune destruction and may be used as a novel preventive strategy for high-risk individuals.

2020-01-30 | GSE144471 | GEO

Stress-induced beta cell dedifferentiation prior to immune cell infiltration prevents type 1 diabetes [Bulk]

2020-01-30 | GSE144461 | GEO

Viral like infection induces Human β cell dedifferentiation

Project description:Viral like infection induces Human β cell dedifferentiation

| PRJNA412009 | ENA

Induction of alpha cell-restricted Gc in dedifferentiating beta cells contributes to stress-induced beta-cell dysfunction [RNA-seq]

Project description:To identify effector genes of pancreatic beta cell dedifferentiation and dysfunction, we performed RNA expression in beta cells sorted from mice with multiparity-induced diabetes.

2019-05-30 | GSE130997 | GEO

Klf6 protects β-cells against insulin resistance-induced dedifferentiation

Project description:Klf6 protects β-cells against insulin resistance-induced dedifferentiation

| PRJNA564774 | ENA