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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE133221 | GEO | 2020/04/15

REPOSITORIES: GEO

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An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells.

Project description:Interferon-α (IFNα), a type I interferon, is expressed in the islets of type 1 diabetic individuals, and its expression and signaling are regulated by T1D genetic risk variants and viral infections associated with T1D. We presently characterize human beta cell responses to IFNα by combining ATAC-seq, RNA-seq and proteomics assays. The initial response to IFNα is characterized by chromatin remodeling, followed by changes in transcriptional and translational regulation. IFNα induces changes in alternative splicing (AS) and first exon usage, increasing the diversity of transcripts expressed by the beta cells. This, combined with changes observed on protein modification/degradation, ER stress and MHC class I, may expand antigens presented by beta cells to the immune system. Beta cells also up-regulate the checkpoint proteins PDL1 and HLA-E that may exert a protective role against the autoimmune assault. Data mining of the present multi-omics analysis identifies two compound classes that antagonize IFNα effects on human beta cells.

| S-EPMC7244579 | biostudies-literature

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]

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

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Integrated multi-omics approach revealed cellular senescence landscape.

Project description:Cellular senescence is a complex multifactorial biological phenomenon that plays essential roles in aging, and aging-related diseases. During this process, the senescent cells undergo gene expression altering and chromatin structure remodeling. However, studies on the epigenetic landscape of senescence using integrated multi-omics approaches are limited. In this research, we performed ATAC-seq, RNA-seq and ChIP-seq on different senescent types to reveal the landscape of senescence and identify the prime regulatory elements. We also obtained 34 key genes and deduced that NAT1, PBX1 and RRM2, which interacted with each other, could be the potential markers of aging and aging-related diseases. In summary, our work provides the landscape to study accessibility dynamics and transcriptional regulations in cellular senescence. The application of this technique in different types of senescence allows us to identify the regulatory elements responsible for the substantial regulation of transcription, providing the insights into molecular mechanisms of senescence.

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

Project description:An integrated multi-omics approach identifies the landscape of interferon-a-mediated responses of human pancreatic beta cells

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Integrated multi-omics approach revealed cellular senescence landscape

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

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

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

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

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

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