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GSE80178
Homo sapiens
4 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Diabetic foot ulcers (DFUs) are the leading cause of lower leg amputations in diabetic population. To better understand molecular pathophysiology of DFUs we used patients specimens and genomic profiling. We identified 3900 genes specifically regulated in DFUs. Moreover, we compared DFU to human skin acute wound (AW) profiles and found DNA repair mechanisms and regulation of gene expression among the processes specifically suppressed in DFUs, whereas essential wound healing-related processes, inflammatory/immune response or cell migration, were not activated properly. To identify potential regulators of DFU-specific genes, we used upstream target analysis. We found miR-15/16 family enriched in DFUs, but not in AW, which was confirmed by qPCR. We found that infection with the most common DFU colonizer, Staphylococcus aureus, triggers induction of miR-15-5p, which in turn, targets multiple DFU-specific genes, including genes involved in DNA repair (WEE1, MSH2 and RAD50) and the regulator of inflammatory pathway, IKBKB. Induction of miR-15b-5p, either by miR-mimic transfection in vitro or by S. aureus infection of acute wounds ex vivo, suppressed both WEE1 and IKBKB. Consequently, we detected an increase in DNA double strand breaks in DFUs. In summary, our data indicate that S. aureus infection, via induction of miR-15b-5p, may lead to suppression of DNA repair mechanisms and a sub-optimal inflammatory response, contributing to pathophysiology of DFU patients
Publication Title
Staphylococcus aureus Triggers Induction of miR-15B-5P to Diminish DNA Repair and Deregulate Inflammatory Response in Diabetic Foot Ulcers.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Plasmacytoid dendritic cells (pDC) efficiently produce large amounts of type I interferon in response to TLR7 and TLR9 ligands, whereas conventional DCs (cDC) predominantly secrete high levels of the cytokines IL-10 and IL-12. The molecular basis underlying this distinct phenotype is not well understood. Here, we identified the MAPK phosphatase Dusp9/MKP-4 by transcriptome analysis as selectively expressed in pDC, but not cDC. We confirmed the constitutive expression of Dusp9 at the protein level in pDC generated in vitro by culture with Flt3L and ex vivo in sorted splenic pDC. Dusp9 expression was low in B220- bone marrow precursors and was up-regulated during pDC differentiation, concomitant with established pDC markers. Higher expression of Dusp9 in pDC correlated with impaired phosphorylation of the MAPK ERK1/2 upon TLR9 stimulation. Notably, Dusp9 was not expressed at detectable levels in human pDC, although these displayed similarly impaired activation of ERK1/2 MAPK compared to cDC. Enforced retroviral expression of Dusp9 in mouse GM-CSF-induced cDC increased the expression of TLR7/9-induced IL-12p40 and IFNwhereas IL-10 levels were diminished. Taken together, our results suggest that the species-specific, selective expression of Dusp9 in murine pDC contributes to the differential cytokine/interferon output of pDC and cDC.
Publication Title
Selective Expression of the MAPK Phosphatase Dusp9/MKP-4 in Mouse Plasmacytoid Dendritic Cells and Regulation of IFN-β Production.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 41 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Inferring causal metabolic signals that regulate the dynamic TORC1-dependent transcriptome.
Sample Metadata Fields
Treatment
View Samples- Saccharomyces cerevisiae
- 14 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Dynamic mRNA gene expression from the wildtype YSBN6 during a nutritional downshift from glutamine to proline. Glutamine and proline were initially together in the media, with cells consuming exlusively glutamine (proline utilization inhibited due to nitrogen catabolite repression). The concentration of glutamine was frequently evaluated at-line, and the moment at which glutamine was not detected anymore is referred to as the time of the shift.
Publication Title
Inferring causal metabolic signals that regulate the dynamic TORC1-dependent transcriptome.
Sample Metadata Fields
Treatment
View Samples- Saccharomyces cerevisiae
- 14 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Dynamic mRNA gene expression from the wildtype YSBN6 during a rapamycin treatment (rapamycin-induced downshift). Rapamycin was added to yeast cells growing exponentially on glutamine as sole nitrogen source.
Publication Title
Inferring causal metabolic signals that regulate the dynamic TORC1-dependent transcriptome.
Sample Metadata Fields
Treatment
View Samples- Saccharomyces cerevisiae
- 13 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Dynamic mRNA gene expression from the wildtype YSBN6 during a nutritional upshift from proline to glutamine. Glutamine was added to yeast cells growing exponentially on proline as the sole nitrogen source.
Publication Title
Inferring causal metabolic signals that regulate the dynamic TORC1-dependent transcriptome.
Sample Metadata Fields
Treatment
View Samples