Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Efferocytic remodeling of pancreatic intra-islet macrophages by limited beta-cell death [scRNASeq_human]

ABSTRACT: The primary driver of Type I diabetes are the autoimmune T cells that destroy insulin-producing beta-cells within the islets of Langerhans in the pancreas. Pancreatic macrophages have also been variably linked to disease onset and progression. As macrophage-mediated removal of dying cells via ‘efferocytosis’ regulate tissue homeostasis and immune responses, we addressed whether efferocytosis by intra-islet macrophages influences the immune environment of pancreatic islets. Here, using a series of complementary omics-based and functional approaches, we identify a subset of anti-inflammatory intra-islet ‘efferocytic macrophages’ (e-Mac) within the pancreas of mice and humans. When limited beta-cell apoptosis is induced in vivo in wild type C57BL/6 mice and diabetic-prone NOD mice, islet macrophages adopt this e-Mac phenotype without an apparent increase in total intra-islet macrophage numbers. Strikingly, such induction of limited beta-cell apoptosis and increase in e-Mac numbers in NOD mice led to long-term suppression of autoimmune diabetes. These data advance a concept that efferocytosis-associated reprogramming of the islet macrophages and its subsequent influence on the adaptive immune response could be beneficial in modulating diabetic autoimmunity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE304620 | GEO | 2025/08/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Efferocytic remodeling of pancreatic intra-islet macrophages by limited beta-cell death [bulk_RNASeq_mouse]

Project description:The primary driver of Type I diabetes are the autoimmune T cells that destroy insulin-producing beta-cells within the islets of Langerhans in the pancreas. Pancreatic macrophages have also been variably linked to disease onset and progression. As macrophage-mediated removal of dying cells via ‘efferocytosis’ regulate tissue homeostasis and immune responses, we addressed whether efferocytosis by intra-islet macrophages influences the immune environment of pancreatic islets. Here, using a series of complementary omics-based and functional approaches, we identify a subset of anti-inflammatory intra-islet ‘efferocytic macrophages’ (e-Mac) within the pancreas of mice and humans. When limited beta-cell apoptosis is induced in vivo in wild type C57BL/6 mice and diabetic-prone NOD mice, islet macrophages adopt this e-Mac phenotype without an apparent increase in total intra-islet macrophage numbers. Strikingly, such induction of limited beta-cell apoptosis and increase in e-Mac numbers in NOD mice led to long-term suppression of autoimmune diabetes. These data advance a concept that efferocytosis-associated reprogramming of the islet macrophages and its subsequent influence on the adaptive immune response could be beneficial in modulating diabetic autoimmunity.

2025-08-09 | GSE304616 | GEO

Efferocytic remodeling of pancreatic intra-islet macrophages by limited beta-cell death

2025-08-09 | GSE304628 | GEO

Transcriptional analysis of type 1 diabetes reveals an interferon signature that precedes T cell activation

Project description:Type 1 diabetes (T1D) is an autoimmune disease triggered by T cell reactivity to protein antigens produced by the β-cells. Here we present a chronological compendium of transcriptional profiles from islets of Langerhans isolated from non-obese diabetic (NOD) mice ranging from 2 wks up to diabetes and compared to controls. Parallel analysis was made of cellular components of the islets. Myeloid cells populated the islets early during development in all mouse strains. This was followed by a type I interferon signature detectable at 4-6 wks of age only in diabetes susceptible mice. Concurrently, CD4 T cells were found within islets, many in contact with intra-islet antigen presenting cells. Early cellular signs of islet reactivity were detected by six wks. By 8 wks, NOD islets contained all major leukocytes populations and an inflammatory gene signature. This work establishes the natural transcriptional signature of T1D and provides a resource for future research. 57 RNA samples isolated from the pancreatic islets of langerhans of experimental mice: 2-18 wk old non-obese diabetic (NOD) and newly diabetic NOD were compared to controls: NOD.RAG-/-, B6.g7 and C57BL/6. There were 3 or 6 biological replicates per condition. All mice were female. All data was normalized using RMA in Arraystar. Data table includes normalized probe intensity for every probe.

2013-01-28 | E-GEOD-41203 | biostudies-arrayexpress

A discovery-based proteomics approach identifies protein disulfide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetes

Project description:Background: Activation of stress pathways intrinsic to the β cell are thought to both accelerate β cell death and increase β cell immunogenicity in type 1 diabetes (T1D). However, information on the timing and scope of these responses is lacking. Methods: To identify temporal and disease-related changes in islet β cell protein expression, SWATH-MS/MS proteomics analysis was performed on islets collected longitudinally from NOD mice and NOD-SCID mice rendered diabetic through T cell adoptive transfer. Findings: In islets collected from female NOD mice at 10, 12, and 14 weeks of age, we found a time-restricted upregulation of proteins involved in the maintenance of β cell function and stress mitigation, followed by loss of expression of protective proteins that heralded diabetes onset. Pathway analysis identified EIF2 signaling and the unfolded protein response, mTOR signaling, mitochondrial function, and oxidative phosphorylation as commonly modulated pathways in both diabetic NOD mice and NOD-SCID mice rendered acutely diabetic by adoptive transfer, highlighting this core set of pathways in T1D pathogenesis. In immunofluorescence validation studies, β cell expression of protein disulfide isomerase A1 (PDIA1) and 14-3-3b were found to be increased during disease progression in NOD islets, while PDIA1 plasma levels were increased in pre-diabetic NOD mice and in the serum of children with recent-onset T1D compared to age and sex-matched non-diabetic controls. Interpretation: We identified a common and core set of modulated pathways across distinct mouse models of T1D and identified PDIA1 as a potential human biomarker of β cell stress in T1D.

2023-03-11 | PXD035504 | Pride

Transcriptional analysis of type 1 diabetes reveals an interferon signature that precedes T cell activation

2013-01-28 | GSE41203 | GEO

RNA sequencing of pancreatic islets and islet-derived macrophages and endothelial cells modulated by vascular endothelial growth factor-A signaling

Project description:Pancreatic islet endocrine cell and endothelial cell (EC) interactions mediated by vascular endothelial growth factor-A (VEGF-A) signaling are important for islet endocrine cell differentiation and the formation of highly vascularized islets. To dissect how VEGF-A signaling modulates intra-islet vasculature and innervation, islet microenvironment, and β cell mass, we transiently increased VEGF-A production by β cells. VEGF-A induction dramatically increased the number of intra-islet ECs but led to β cell loss. After withdrawal of the VEGF-A stimulus, β cell mass, function, and islet structure normalized as a result of a robust, but transient, burst in proliferation of pre-existing β cells. Bone marrow-derived macrophages (MΦs) recruited to the site of β cell injury were crucial for the β cell proliferation, which was independent of pancreatic location and circulating factors such as glucose. Identification of the signals responsible for the proliferation of adult, terminally differentiated β cells will improve strategies aimed at β cell regeneration and expansion. Examination of RNA profiles from isolated whole islets from RIP-rtTA; TetO-VEGF-A mice with no doxycycline (Dox) treatment (3 samples) and after 1 week of Dox (3 sample); and islet-derived macrophages (3 samples) and endothelial cells (3 samples) isolated from dispersed purified islets from RIP-rtTA; TetO-VEGF-A mice after 1 week Dox treatment by fluorescence-activated cell sorting using antibodies against CD11b and CD31, respectively.

2015-09-01 | E-GEOD-72546 | biostudies-arrayexpress

Genome-wide effect of islet isolation and in vitro culture on gene expression profile of pancreatic beta-cells enriched tissue.

Project description:It is known that the stresses encountered during islet isolation have deleterious effects on beta-cell physiology. The nature of these effects, however, is incompletely known, partly due to the heterogeneity of islet preparations. The objective was to assess the genome-wide effect of islet isolation and in-vitro culture on beta-cell transcriptome. Beta cells identified by their intrinsic autofluorescence, were captured from donor pancreas and isolated islets using Laser Capture Microdissection. Beta cells from donor pancreas serve as the control. Our results indicated induction of a strong inflammatory response induced by islet isolation which continues during in vitro culture manifested by upregulation of several cytokines, chemokines and their receptors. IL-8 was induced by 3.6-fold and 56-fold in fresh and 3-days cultured islets respectively. Concordantly, several pancreatic progenitor cell-specific transcription factors like were upregulated in cultured islets, suggesting progressive transformation of mature beta-cell phenotype toward an immature endocrine cell phenotype. There are three sample types in our experiment; 1) beta-cells captured from the frozen sections of donor pancreas n=8, 2) beta cells extracted from islets frozen immediately after isolation (d0 islets) n=8 and, 3) beta cells extracted from isolated islets frozen after culturing for 3 days (d3 islets) n=5. For the analysis, beta cells from pancreas were considered as the reference point.

2012-02-12 | E-GEOD-29113 | biostudies-arrayexpress

Proteome and (ox)PTP profile analysis of diabetic NOD mouse under single (anti-CD3) or combined (anti-CD3 + IL1RA) treatment

Project description:Type 1 diabetes (T1D) results from autoimmune destruction of β cells in the pancreas. Protein tyrosine phosphatases (PTPs) are candidate genes for T1D and play a key role in autoimmune disease development and β-cell function. Here, we assessed the global protein and individual PTP profile in the pancreas of diabetic NOD mice treated with anti-CD3 mAb and IL-1RA combination therapy. The treatment reversed hyperglycemia compared to the anti-CD3 alone control group. We observed enhanced expression of PTPN2, a T1D candidate gene, and endoplasmic reticulum (ER) chaperones in the islets from cured mice.

2022-11-10 | PXD025394 | Pride

Endocrine cell type sorting and mature architecture in the islets of Langerhans require expression of Roundabout receptors in β cells

Project description:The spatial architecture of the islets of Langerhans is hypothesized to facilitate synchronized insulin secretion among β cells, yet testing this in vivo in the intact pancreas is challenging. Robo βKO mice, in which the genes Robo1 and Robo2 are deleted selectively in β cells, provide a unique model of altered islet spatial architecture without loss of β cell differentiation or islet damage from diabetes. Combining Robo βKO mice with intravital microscopy, we show here that Robo βKO islets have reduced synchronized intra-islet Ca2+ oscillations among β cells in vivo. We provide evidence that this loss is not due to a β cell-intrinsic function of Robo, mis-expression or mis-localization of Cx36 gap junctions, or changes in islet vascularization or innervation, suggesting that the islet architecture itself is required for synchronized Ca2+ oscillations. These results have implications for understanding structure-function relationships in the islets during progression to diabetes as well as engineering islets from stem cells.

2024-08-26 | GSE275474 | GEO

Expression data from type 2 diabetic and non-diabetic isolated human islets

Project description:We performed microarray analysis to evaluate differences in the transcriptome of type 2 diabetic human islets compared to non-diabetic islet samples. Human islets were isolated from the pancreas of organ donors by collagenase digestion followed by density gradient purification, then hand-picked and cultured 2 days in M199 culture medium.

2010-12-01 | E-GEOD-25724 | biostudies-arrayexpress

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