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GSE90450
Mus musculus
20 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Tristetraprolin (TTP, encoded by Zfp36) regulates the mRNA stability of several important cytokines. Due to the critical role of this RNA-binding protein in the control of inflammation, TTP deficiency leads to the spontaneous development of a complex inflammatory syndrome. So far, this phenotype has been largely attributed to dysregulated production of TNF and IL-23 by myeloid cells such as macrophages or dendritic cells. Here, we generated mice with conditional deletion of TTP in keratinocytes. These mice developed exacerbated inflammation in the imiquimod-induced psoriasis model. Furthermore, these mice progressively developed a spontaneous pathology with systemic inflammation, psoriatic-like skin lesions and dactylitis. Finally, we provide evidence that keratinocyte-derived TNF productin drives the different pathological features. In summary, these findings expand current views on the initiation of psoriasis and related arthritis by revealing the keratinocyte-intrinsic role of TTP.
Publication Title
Tristetraprolin expression by keratinocytes controls local and systemic inflammation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Stellate Cells, Hepatocytes, and Endothelial Cells Imprint the Kupffer Cell Identity on Monocytes Colonizing the Liver Macrophage Niche.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Macrophages are strongly adapted to their tissue of residence. Yet, we know little about the cell-cell interactions that imprint the tissue-specific identities of macrophages in their respective niches. Using conditional depletion of liver Kupffer cells, we traced the developmental stages of monocytes differentiating into Kupffer cells and mapped the cellular interactions imprinting the Kupffer cell identity. Kupffer cell loss induced the tumor necrosis factor (TNF) and interleukin-1 (IL-1) receptor-dependent activation of stellate cells and endothelial cells, resulting in the transient production of chemokines and adhesion molecules orchestrating monocyte engraftment. Engrafted circulating monocytes transmigrated into the perisinusoidal space, and acquired the liver-associated transcription factors ID3 and LXRα. Coordinated interactions with hepatocytes induced ID3 expression, while endothelial cells and stellate cells induced LXRα via a synergistic NOTCH-BMP pathway. This study shows that the Kupffer cell niche is composed of stellate cells, hepatocytes and endothelial cells that together imprint the liver-specific macrophage identity.
Publication Title
Stellate Cells, Hepatocytes, and Endothelial Cells Imprint the Kupffer Cell Identity on Monocytes Colonizing the Liver Macrophage Niche.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 43 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Foxl2 functions in sex determination and histogenesis throughout mouse ovary development.
Sample Metadata Fields
Sex, Subject
View Samples- Mus musculus
- 43 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Comparison of Foxl2-null ovaries to wildtype ovaries, ovaries lacking Wnt4 or Kit, or testes, throughout mouse development.
Publication Title
Foxl2 functions in sex determination and histogenesis throughout mouse ovary development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The role of Tfr1 in non-erythroid tissues remains elusive due to the embryonic lethality of the Tfr1 global knockout mouse model. To bypass this problem, we generated a mouse model in which Tfr1 was conditionally deleted in intestinal epithelial cells (IECs). These mice developed severe IEC disruption, characterized by blunted villi, edema, loss of proliferative intervillus IECs, accumulation of lipids, and early neonatal lethality. Strikingly, a wide range of genes associated with epithelial-to-mesenchymal transition were highly upregulated in IEC lacking Tfr1. Additionally, candidate vesicular transport and sorting genes implicated in lipid absorption and trafficking were downregulated. Surprisingly, the presence of a mutant allele of Tfr1, which is unable to bind to iron-loaded transferrin, was capable of rescuing the lethality, intestinal epithelial homeostasis, and proliferation in a majority of the Tfr1 conditional knockout mice.
Publication Title
Noncanonical role of transferrin receptor 1 is essential for intestinal homeostasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While the transcriptional program that initiates adipogenesis is well-known, the importance of microRNAs in adipogenesis is less well studied. We thus set out to investigate whether miRNAs would be actively modulated during adipogenesis and obesity. Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is probably the most well known, albeit not the most physiologically appropriate. We used a microarray strategy to provide a global profile of miRNAs in brown and white primary murine adipocytes (prior to and following differentiation) and evaluated the similarity of the responses to non-primary cell models, through literature data-mining. We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. When we compared our primary adipocyte profiles with those of cell lines reported in the literature, we found a high degree of difference in adipogenesis-regulated miRNAs. We evaluated the expression of 10 of our adipogenesis-regulated miRNAs using real-time qPCR and then selected 5 miRNAs that showed robust expression levels and profiled these by qPCR in subcutaneous adipose tissue of 20 humans with a range of body mass indices (BMI, range=21-48). Of the miRNAs tested, mir-21 was both highly expressed in human adipose tissue and positively correlated with BMI (R2=0.49, p<0.001). In conclusion, we provide the preliminary analysis of miRNAs important for primary cell in vitro adipogenesis and find that the inflammation-associated miRNA, mir-21, is up-regulated in subcutaneous adipose tissue in human obesity.
Publication Title
Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity.
Sample Metadata Fields
Age
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
To examine changes in gene expression that might occur in CNS glial cells in response to the secreted products of immune cells, we used gene array analysis to assess the early effects of different cytokine mixtures on rat mixed CNS glia in culture. We compared effects at 6 hours of cytokines typical of Th1 and Th2 lymphocytes, and monocyte marophages (M/M).. We found unique patterns of changes in gene expression for each of the three cytokine mixtures, including changes in immune-related molecules, neurotrophins, growth factors, proteins involved in axon/glial interactions, ion channels, neurotransmitters, mitochondrial function and apoptosis. These changes may have relevance in neuroprotective or damaging mechanisms in neurodegenerative diseases such as multiple sclerosis, specifically with regard to formation, repair or inhibition of lesion formation.
Publication Title
Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptional programming of cell identity promises to open up new frontiers in regenerative medicine by enabling the efficient production of clinically relevant cell types. We examine if such cellular programming is accomplished by transcription factors that each have an independent and additive effect on cellular identity, or if programming factors synergize to produce an effect that is not independently obtainable. The combinations of Ngn2-Isl1-Lhx3 and Ngn2-Isl1-Phox2a transcription factors program embryonic stem cells to express a spinal or cranial motor neuron identity respectively. The two alternate expression programs are determined by recruitment of Isl1/Lhx3 and Isl1/Phox2a pairs to distinct genomic locations characterized by two alternative dimeric homeobox motifs. These results suggest that the function of programming modules relies on synergistic interactions among transcription factors and thus cannot be extrapolated from the study of individual transcription factors in a different cellular context.
Publication Title
Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity.
Sample Metadata Fields
Cell line, Treatment
View Samples