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accession-icon SRP177950
Epigenetic modulation of ß-cells by interferon-a via PNPT11-miR-26a-TET2 triggers autoimmune diabetes [RNA-seq]
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

Type 1 diabetes (T1D) is caused by autoimmune destruction of pancreatic ß cells. Mounting evidence supports a central role for ß-cell alterations in triggering the activation of self-reactive T-cells in T1D. However, the early deleterious events that occur in ß cells, underpinning islet autoimmunity are not known. We hypothesized that epigenetic modifications induced in ß cells by inflammatory mediators play a key role in initiating the autoimmune response. We analyzed DNA methylation (DNAm) patterns and gene expression in human islets exposed to IFNa, a cytokine associated with T1D development. We found that IFNa triggers DNA demethylation and increases expression of genes controlling inflammatory and immune pathways. We then demonstrated that DNA demethylation was caused by up-regulation of the exoribonuclease, PNPase Old-35 (PNPT1), which caused degradation of miR-26a. This in turn promoted the up-regulation of ten-eleven translocation TET2 enzyme and increased 5-hydoxymethylcytosine levels in human islets and pancreatic ß-cells. Moreover, we showed that specific IFNa expression in the ß cells of IFNa-INS1CreERT2 transgenic mice, led to development of T1D that was preceded by increased islet DNA hydroxymethylation through a PNPT1/TET2-dependent mechanism. Our results suggest a new mechanism through which IFNa regulates DNAm in ß cells, leading to changes in expression of genes in inflammatory and immune pathways that can initiate islet autoimmunity in T1D. Overall design: We exposed human pancreatic islets from three donors to 2000 IU IFNa and assessed gene expression by RNAseq. The cDNA library was prepared using Illumina TruSeq RNA Sample Prep Kits. Next generation sequencing was performed on Illumina HiSeq2000 using the Single-Read Cluster Generation kit v2 and SBS Sequencing kit v3. Image analysis and base calling were conducted using the SDS 2.5/RTA1.5 software.

Publication Title

Epigenetic modulation of β cells by interferon-α via PNPT1/mir-26a/TET2 triggers autoimmune diabetes.

Sample Metadata Fields

Specimen part, Disease stage, Treatment, Subject

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accession-icon SRP034556
Ikaros mutation confers integrin-dependent pre-B cell survival and progression to acute lymphoblastic leukemia
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer

Description

Deletion of the Ikaros DNA-binding domain generates dominant-negative isoforms that interfere with Ikaros family activity and correlate with poor prognosis in human precursor B cell acute lymphoblastic leukemias (B-ALL).  Here, we show that conditional inactivation of the Ikaros DNA binding domain in early pre-B cells arrests their differentiation at a stage where integrin-dependent niche adhesion augments mitogen-activated protein kinase signaling, proliferation, and self-renewal, and attenuates pre-B cell receptor signaling and differentiation. Transplantation of polyclonal Ikzf1 mutant pre-B cells results in long-latency oligoclonal pre-B-ALL, demonstrating that loss of Ikaros contributes to multistep B-leukemogenesis. These results explain how normal pre-B cells transit from a highly proliferative and stromal-dependent to a stromal-independent phase where differentiation is enabled, providing potential therapeutic strategies for IKZF1 mutant B-ALL.   Overall design: One of the analyses described in this manuscript is the differential gene expression of large preB cells sorted from the bone marrow of WT and IKDN mice. The RNASeq method and Deseq analysis algorithm were employed

Publication Title

Loss of Ikaros DNA-binding function confers integrin-dependent survival on pre-B cells and progression to acute lymphoblastic leukemia.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE33121
Expression data from ESC and in vitro derived somatic cells and germ cells
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

We performed gene expression profiling on in vitro derived PGCs, undifferentiated ESCs, and somatic cells from the EB to examine germ cell expression in ESC-derived cells

Publication Title

Single cell analysis facilitates staging of Blimp1-dependent primordial germ cells derived from mouse embryonic stem cells.

Sample Metadata Fields

Specimen part

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accession-icon GSE117463
Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice
  • organism-icon Mus musculus
  • sample-icon 23 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

Description

Human mucosal surfaces contain a wide range of microorganisms. The biological effects of these organisms are largely unknown. Large-scale metagenomic sequencing is emerging as a method to identify novel microbes. Unexpectedly, we identified DNA sequences homologous to virus ATCV-1, an algal virus not previously known to infect humans, in oropharyngeal samples obtained from healthy adults. The presence of ATCV-1 was associated with a modest but measurable decrease in cognitive functioning. A relationship between ATCV-1 and cognitive functioning was confirmed in a mouse model, which also indicated that exposure to ATCV-1 resulted in changes in gene expression within the brain. Our study indicates that viruses in the environment not thought to infect humans can have biological effects.

Publication Title

Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice.

Sample Metadata Fields

Treatment

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accession-icon GSE59949
Expression data from human dental follicle cells
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.1 ST Array (hugene11st)

Description

We analysed the genexpression of dental follicle cells (DFCs) after 3 days osteogenic differentiation with BMP2 after transfection with a DLX3 plasmid (pDLX3) and after transfection with an empty plasmid (pEV)

Publication Title

A protein kinase A (PKA)/β-catenin pathway sustains the BMP2/DLX3-induced osteogenic differentiation in dental follicle cells (DFCs).

Sample Metadata Fields

Specimen part

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accession-icon GSE14067
Kidney transplantation
  • organism-icon Homo sapiens
  • sample-icon 72 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

In this study, we examined transcriptional profiles from 3 different microarray platforms, across 103 peripheral blood samples with and without acute rejection, to find a critical gene-set for the diagnosis of acute renal rejection that matched biopsy diagnosis, irrespective of patient demographics, clinical confounders, concomitant infection, immunosuppression usage or sample processing methods. We hypothesized that changes in peripheral blood expression profiles correlate with biopsy-proven rejection, and that these changes could be used as biomarkers for the diagnosis and prediction of acute rejection.

Publication Title

A peripheral blood diagnostic test for acute rejection in renal transplantation.

Sample Metadata Fields

Disease, Disease stage

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accession-icon GSE14346
Kidney transplantation (Affymetrix set)
  • organism-icon Homo sapiens
  • sample-icon 72 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

In this study, we examined transcriptional profiles from 3 different microarray platforms, across 103 peripheral blood samples with and without acute rejection, to find a critical gene-set for the diagnosis of acute renal rejection that matched biopsy diagnosis, irrespective of patient demographics, clinical confounders, concomitant infection, immunosuppression usage or sample processing methods. We hypothesized that changes in peripheral blood expression profiles correlate with biopsy-proven rejection, and that these changes could be used as biomarkers for the diagnosis and prediction of acute rejection.

Publication Title

A peripheral blood diagnostic test for acute rejection in renal transplantation.

Sample Metadata Fields

Disease, Disease stage

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accession-icon GSE18975
Natural variation of auxin response
  • organism-icon Arabidopsis thaliana
  • sample-icon 83 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

To assess natural variation of downstream auxin responses we subjected 7 different arabidopsis ecotypes to a time course of auxin treatments. 7d-old seedlings grown in liquid culture have been treated for 0, 30 min, 1h and 3h with 1 M IAA.

Publication Title

Natural variation of transcriptional auxin response networks in Arabidopsis thaliana.

Sample Metadata Fields

Specimen part

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accession-icon GSE109248
Genome-wide analysis of gene expression of cutaneous lupus and cutaneous psoriasis lesions
  • organism-icon Homo sapiens
  • sample-icon 56 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

Human skin samples from cutaneous lupus subtypes, psoriasis, and normal patients were used to corroborate findings of Fas Ligand elevation in a murine model of cutaneous lupus

Publication Title

Fas ligand promotes an inducible TLR-dependent model of cutaneous lupus-like inflammation.

Sample Metadata Fields

Specimen part, Disease, Disease stage

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accession-icon GSE74266
Gene expression profiling in DLBCL primary clinical samples
  • organism-icon Homo sapiens
  • sample-icon 61 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Gene expression profiling was performed for 28 DLBCL primary clinical samples and assignment of activated B-cell-like(ABC)/germinal center B-cell-like (GCB) DLBCL classes, B-cell-associated gene signature (BAGS), and a probability of response to doxorubicin was performed for each sample.

Publication Title

High miR-34a expression improves response to doxorubicin in diffuse large B-cell lymphoma.

Sample Metadata Fields

Specimen part, Disease stage, Treatment

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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