Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcription and splicing regulation by NLRC5 shape the interferon response in human pancreatic β-cells [RNA-seq]

ABSTRACT: IFNa is a key regulator of the dialogue between pancreatic β-cells and the immune system in early type 1 diabetes (T1D). IFNa up-regulates HLA class I expression in human β-cells fostering autoantigen presentation to the immune system. We observed by bulk and single cell RNA sequencing that exposure of human induced pluripotent-derived islet-like cells to IFNa induces expression of HLA class I and of other genes involved in antigen presentation, including the transcriptional activator NLRC5. We next evaluated the global role of NLRC5 in human insulin-producing EndoC-βH1 and human islets cells by RNA sequencing and targeted gene/protein determination. NLRC5 regulates expression of HLA class I expression and related genes and of chemokines. NLRC5 also mediates the effects of IFNa on alternative splicing, a generator of β-cell neoantigens, suggesting that it is a central mediator of the effects of IFNa on β-cells that contribute to trigger and amplify autoimmunity in T1D.

ORGANISM(S): Homo sapiens

PROVIDER: GSE202852 | GEO | 2022/09/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription and splicing regulation by NLRC5 shape the interferon response in human pancreatic β-cells [iPSC scRNAseq]

Project description:IFNa is a key regulator of the dialogue between pancreatic β-cells and the immune system in early type 1 diabetes (T1D). IFNa up-regulates HLA class I expression in human β-cells fostering autoantigen presentation to the immune system. We observed by bulk and single cell RNA sequencing that exposure of human induced pluripotent-derived islet-like cells to IFNa induces expression of HLA class I and of other genes involved in antigen presentation, including the transcriptional activator NLRC5. We next evaluated the global role of NLRC5 in human insulin-producing EndoC-βH1 and human islets cells by RNA sequencing and targeted gene/protein determination. NLRC5 regulates expression of HLA class I expression and related genes and of chemokines. NLRC5 also mediates the effects of IFNa on alternative splicing, a generator of β-cell neoantigens, suggesting that it is a central mediator of the effects of IFNa on β-cells that contribute to trigger and amplify autoimmunity in T1D.

2022-09-14 | GSE203384 | GEO

Transcription and splicing regulation by NLRC5 shape the interferon response in human pancreatic β-cells [iPSC bulk RNAseq]

Project description:IFNa is a key regulator of the dialogue between pancreatic β-cells and the immune system in early type 1 diabetes (T1D). IFNa up-regulates HLA class I expression in human b-cells fostering autoantigen presentation to the immune system. We observed by bulk and single cell RNA sequencing that exposure of human induced pluripotent-derived islet-like cells to IFNa induces expression of HLA class I and of other genes involved in antigen presentation, including the transcriptional activator NLRC5. We next evaluated the global role of NLRC5 in human insulin-producing EndoC-bH1 and human islets cells by RNA sequencing and targeted gene/protein determination. NLRC5 regulates expression of HLA class I expression and related genes and of chemokines. NLRC5 also mediates the effects of IFNa on alternative splicing, a generator of β-cell neoantigens, suggesting that it is a central mediator of the effects of IFNa on β-cells that contribute to trigger and amplify autoimmunity in T1D.

2022-09-14 | GSE203430 | GEO

HLA Class II analysis of human pancreatic beta cells

Project description:We interrogated the transcriptome from bulk-sorted T1D donor β-cells as compared to non-diabetic donors. We found β-cells also expressed mRNA for HLA Class II and Class II antigen presentation pathway components, but not a macrophage marker.

2019-03-01 | GSE121863 | GEO

Targeted demethylation and activation of NLRC5 augments cancer immunogenicity through MHC class I

Project description:Impaired expression of MHC class I constitutes a major mechanism of immune evasion of cancers, leading to poor prognosis and resistance to checkpoint blockade therapies. Existing drugs for MHC class I have limited applicability due to severe side effects. Here we show a novel approach of robust and specific induction of MHC class I by targeting an MHC class I transactivator (CITA), NLRC5, using a CRISPR/Cas9 based gene-specific targeted demethylaion (TDM) system and targeted demethylation and activation (TDMa) system. The TDMa system specifically recruits a demethylating enzyme and transcriptional activators, providing efficient demethylation and transactivation of the NLRC5 promoter. TDMa in mouse and human cancer cells induced MHC class I antigen presentation and accelerated CD8+ T cell activation with tumor suppression effects both in vitro and in vivo. Moreover, enhanced immunogenicity by NLRC5 TDMa boosted efficacy of anti-PD1 therapy. Therefore, NLRC5 targeting by the TDMa system confers an attractive therapeutic approach against cancer.

2024-02-22 | GSE233194 | GEO

An integrated multi-omics approach identifies the landscape of interferon-a-mediated responses of human pancreatic beta cells [ATAC-seq]

Project description:Proinflammatory cytokines are important mediators of pancreatic beta cell dysfunction and demise in type 1 diabetes (T1D). We presently characterized human beta cell responses to IFNa by combining ATAC-seq, RNA-seq and proteomics assays. The initial beta cell response to IFNa was characterized by major chromatin remodeling, followed by marked changes in transcriptional and translational regulation. IFNa-induced changes in alternative splicing (AS) and first exon usage increased the diversity of transcripts expressed by beta cells. This, combined with changes observed on protein modification/degradation, ER stress and MHC class I, may significantly expand the peptide repertoire presented by beta cells to the immune system. On the other hand, beta cells up-regulated checkpoint proteins, such as PDL1 and HLA-E, that may protect them against the autoimmune assault. Data mining of the present multi-omics analysis led to the identification of two compound classes that revert IFNa effects on human beta cells and may be translated to clinical trials.

2020-04-15 | GSE133219 | GEO

An integrated multi-omics approach identifies the landscape of interferon-a-mediated responses of human pancreatic beta cells [RNA-seq]

2020-04-15 | GSE133218 | GEO

An integrated multi-omics approach identifies the landscape of interferon-a-mediated responses of human pancreatic beta cells [RNA-seq 2]

2020-04-15 | GSE148058 | GEO

NLRC5 specifically transactivates MHC class I and related genes through a distinctive SXY module

Project description:MHC class II (MHCII) genes are transactivated by the NOD-like receptor (NLR) factor CIITA, which is recruited to SXY regulatory modules of MHC promoters via a DNA-binding “enhanceosome” complex. NLRC5, another NLR protein, was recently found to control transcription of MHC class I (MHCI) genes. However, detailed understanding of its target-gene specificity and mechanism of action remained lacking. We therefore performed ChIP-sequencing experiments to gain comprehensive information on NLRC5-transactivated genes. In addition to classical MHCI genes, we identified novel NLRC5-targets exclusively in the H2-Q and H2-T regions of the MHCI locus, among which the best targets were found. Investigation of cells lacking the MHCII-enhanceosome factor RFX5 demonstrated its strict requirement for NLRC5 recruitment to the SXY module conserved in MHCI genes. Furthermore, patient-derived B cell lines deficient in RFX5, RFXAP, and RFXANK corroborated importance of the enhanceosome for MHCI transactivation. Although sharing similar SXY modules and common DNA-binding factors, CIITA and NLRC5 regulate distinct genes, as shown here using double-deficient Nlrc5-/-CIIta-/- mice. The identification of sequences occupied by NLRC5 in vivo allowed us to define a unique consensus motif for its recruitment, which diverges from that used by CIITA. Our results thus broaden our knowledge on transcriptional activity of NLRC5, highlighting its remarkable selectivity for genes encoding MHCI or related proteins and providing insights into the specificity of its recruitment. Analysis of Nlrc5 binding sites in T-cells

2015-02-27 | E-GEOD-59092 | biostudies-arrayexpress

Expression data from PolyIC treated EndoC-ßH1 cells

Project description:Type 1 diabetes (T1D) is a chronic disease characterized by an autoimmune-mediated destruction of insulin-producing pancreatic β cells. Environmental factors such as viruses play an important role in the onset of T1D and interact with predisposing genes. Recent data suggest that viral infection of human islets leads to a decrease in insulin production rather than β cell death, suggesting loss of β cell identity. We undertook this study to examine whether viral infection could induce human ß cell dedifferentiation. Using the functional human β cell line EndoC-βH1, we demonstrate that polyinosinic-polycitidilic acid (PolyI:C), a synthetic double-stranded RNA that mimics a by-product of viral replication induces a decrease in β cell-specific gene expression. In parallel to this loss, the expression of progenitor-like genes such as SOX9 was activated following PolyI:C treatment or enteroviral infection. SOX9 was induced by the NF-kB pathway and also in a paracrine non-cell autonomous fashion through the secretion of IFNA. Finally, we identified new SOX9 targets in human β cells as new markers of dedifferentiation in T1D. These findings reveal that inflammatory signaling has clear implications in human β cell dedifferentiation.

2018-01-31 | GSE104190 | GEO

NLRC5 deficiency protects against acute kidney injury in mice by mediating CEACAM1 signaling

Project description:Although there is significant progress in understanding the structure and function of NLRC5, a member of the NOD like receptor (NLR) family, in the context of MHC class I gene expression, the functions of NLRC5 in innate and adaptive immune responses beyond the regulation of MHC class I genes remain controversial and unresolved. In particular, the role of NLRC5 in the kidney keeps unknown. In this study, we found that NLRC5 was significantly upregulated in the kidney from mice with renal ischemia/reperfusion injury (IRI). NLRC5 deficient (NLRC5-/-) mice significantly ameliorated renal injury as evidenced by decreased serum creatinine levels, improved morphological injuries, and reduced inflammatory responses versus wild type mice. Similar protective effects were also observed in cisplatin-induced acute kidney injury (AKI). Mechanistically, NLRC5 contributed to renal injury by promoting tubular epithelial cell apoptosis and reducing inflammatory responses which is associated with, at least in part, the negative regulation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). To determine the relative contribution of NLRC5 expression by parenchymal cells or leukocytes to renal damage during IRI, we generated bone marrow (BM) chimeric mice. NLRC5-/- mice engrafted with WT hematopoietic cells had significantly lower serum creatinine and less tubular damage than WT mice reconstituted with NLRC5-/- BM, suggesting that NLRC5 signaling in renal parenchymal cells plays the dominant role in mediating renal damage. Collectively, modulation of NLRC5-mediated pathway may have important therapeutic implications for patients with AKI.

2018-01-19 | GSE109374 | 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