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

ABSTRACT: Stress-induced beta cell dedifferentiation prior to immune cell infiltration prevents type 1 diabetes

PROVIDER: PRJNA603746 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10984855.fastq.gz	Fastqsanger.gz
	SRR10984856.fastq.gz	Fastqsanger.gz
	SRR10984857.fastq.gz	Fastqsanger.gz
	SRR10984858.fastq.gz	Fastqsanger.gz
	SRR10984859.fastq.gz	Fastqsanger.gz

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

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

| PRJNA603743 | ENA

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

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

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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

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-01-30 | GSE144472 | GEO

Increased β-cell proliferation prior to immune-cell invasion prevents progression of type 1 diabetes

Project description:Type 1 diabetes (T1D) is characterized by pancreatic islet infiltration by autoreactive immune cells and a near-total loss of β-cells. Restoration of insulin-producing β-cells coupled with immunomodulation to suppress the autoimmune attack has emerged as a potential approach to counter T1D. Here we report that enhancing β-cell mass in female NOD mice early in life (prior to weaning) results in immunomodulation of T-cells, reduced islet infiltration and lower β-cell apoptosis, that together protect them from developing T1D. We observed that a model exhibiting β-cell hyperplasia on the NOD background (NOD-LIRKO) displayed altered β-cell antigens, and islet transplantation studies showed prolonged graft survival of NOD-LIRKO islets even upon exposure to diabetogenic splenocytes in vivo. Adoptive transfer of splenocytes from the NOD-LIRKOs prevented diabetes development in pre-diabetic NOD mice, while conversely, similar protective outcomes were obtained when NOD-LIRKO splenocytes were adoptively transferred after mixing them with diabetogenic NOD splenocytes in a dose-dependent manner. A significant increase in the splenic CD4+CD25+FoxP3+ regulatory T-cell (Treg) population in the NOD-LIRKO mice was observed to drive the protected phenotype since Treg depletion rendered NOD-LIRKO mice diabetic. The increase in Tregs coupled with a downregulation of key mediators of cellular function, upregulation of apoptosis and activation of TGF-β/SMAD3 signaling pathway in pathogenic T-cells favored reduced ability to kill β-cells. These data provide novel evidence that initiating β-cell proliferation, alone, prior to islet infiltration by immune cells alters the identity of β-cells, decreases pathologic self-reactivity of effector cells and increases Tregs to prevent progression of T1D.

2019-03-29 | GSE128315 | GEO

Increased β-cell proliferation prior to immune-cell invasion prevents progression of type 1 diabetes

Project description:Increased β-cell proliferation prior to immune-cell invasion prevents progression of type 1 diabetes

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Beta Cell Dedifferentiation Induced by IRE1α Deletion Prevents Type 1 Diabetes.

Project description:Immune-mediated destruction of insulin-producing β cells causes type 1 diabetes (T1D). However, how β cells participate in their own destruction during 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 by deleting the UPR sensor IRE1α prior to insulitis induced a transient dedifferentiation of β cells, resulting in substantially reduced islet immune cell infiltration and β cell apoptosis. Single-cell and whole-islet transcriptomics analyses of immature β cells revealed remarkably diminished expression of β cell autoantigens and MHC class I components, and upregulation of immune inhibitory markers. IRE1α-deficient mice exhibited significantly fewer cytotoxic CD8+ T cells in their pancreata, and adoptive transfer of their total T cells did not induce diabetes in Rag1-/- mice. Our results indicate that inducing β cell dedifferentiation, prior to insulitis, allows these cells to escape immune-mediated destruction and may be used as a novel preventive strategy for T1D in high-risk individuals.

| S-EPMC7346095 | biostudies-literature

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

HIRA regulate Arabidopsis dedifferentiation process

Project description:Plant development is characterised by the capacity to reprogram differentiated cells to initiate asexual reproduction and to produce new organs such as lateral roots. To test whether HIRA could be involved in aspects of developmental reprogramming we studied the effect of HIRA during de-differentiation Arabidopsis root tissue was digested with enzyme to generate protoplast. This process would induce plant cell dedifferentiation. Experiments were performed in WT and hira background to understand how hira affect plant dedifferentiation process.

2014-10-01 | E-GEOD-57044 | biostudies-arrayexpress

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