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GSE14769
Mus musculus
19 Downloadable Samples
Description
The innate immune system is a two-edged sword; it is absolutely required for host defense against infection, but if left uncontrolled can trigger a plethora of inflammatory diseases. Here we used systems biology approaches to predict and validate a gene regulatory network involving a dynamic interplay between the transcription factors NF-B, C/EBP, and ATF3 that controls inflammatory responses. We mathematically modeled transcriptional regulation of Il6 and Cebpd genes and experimentally validated the prediction that the combination of an initiator (NF-B), an amplifier (C/EBP) and an attenuator (ATF3) forms a regulatory circuit that discriminates between transient and persistent Toll-like receptor 4-induced signals. Our results suggest a mechanism that enables the innate immune system to detect the duration of infection and to respond appropriately.
Publication Title
Function of C/EBPdelta in a regulatory circuit that discriminates between transient and persistent TLR4-induced signals.
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Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
Description
Hypertrophic scar (HTS) formation is characterized by exuberant fibroproliferation for reasons that remain poorly understood1. One important but often overlooked component of wound repair is mechanical force, which regulates reciprocal cell-matrix interactions through focal adhesion components including focal adhesion kinase (FAK)1,2. Here we report that FAK is activated following cutaneous injury and that this activation is potentiated by mechanical loading. Transgenic mice lacking fibroblast-specific FAK exhibit significantly less fibrosis in a preclinical model of HTS formation. Inflammatory pathways involving monocyte chemoattractant protein-1 (MCP-1), a chemokine highly implicated in human skin fibrosis3, are triggered following FAK activation, mechanistically linking physical force to fibrosis. Further, small molecule inhibition of FAK effectively abrogates fibroproliferative mechanisms in human cells and significantly reduces scar formation in vivo. Collectively, these findings establish a molecular basis for HTS formation based on the mechanical activation of fibroblast-specific FAK and demonstrate the therapeutic potential of targeted mechanomodulatory strategies.
Publication Title
Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling.
Alternate Accession IDs
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The gene expression of bone marrow cells of mice enriched for
Publication Title
Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential.
Alternate Accession IDs
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 42 Downloadable Samples
Description
Transcriptome analysis of mRNA samples from a cohort of mice with histopathologically diagnosed Undifferentiated Myeloid Leukemia.
Publication Title
Analyzing tumor heterogeneity and driver genes in single myeloid leukemia cells with SBCapSeq.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
Description
PTEN loss or PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, in preclinical murine models, deletion of Pten alone fails to mimic the significant metastatic burden that frequently accompanies the end stage of human disease. To identify additional pathway alterations that cooperate with PTEN loss in prostate cancer progression, we surveyed human prostate cancer tissue microarrays and found that the RAS/MAPK pathway is significantly elevated both in primary and metastatic lesions. In an attempt to model this event, we crossed conditional activatable K-rasG12D/WT mice with the prostate conditional Pten deletion model we previously generated. Although RAS activation alone cannot initiate prostate cancer development, it significantly accelerated progression caused by PTEN loss, accompanied by epithelial-to-mesenchymal transition (EMT) and macrometastasis with 100% penitence. A novel stem/progenitor subpopulation with mesenchymal characteristics was isolated from the compound mutant prostates, which was highly metastatic upon orthotopic transplantation. Importantly, inhibition of RAS/MAPK signaling by PD325901, a MEK inhibitor, significantly reduced the metastatic progression initiated from transplanted stem/progenitor cells. Collectively, these data indicate that activation of RAS/MAPK signaling serves as a potentiating second hit to alteration of the PTEN/PI3K/AKT axis and co-targeting both pathways is highly effective in preventing the development of metastatic prostate cancers.
Publication Title
Pten loss and RAS/MAPK activation cooperate to promote EMT and metastasis initiated from prostate cancer stem/progenitor cells.
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Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
Description
The purpose was to determine AcP- and AcPb-dependent gene responses to IL-1 by virally-reconstituting AcP-deficient mouse embryonic cortical neurons with CD25 (control), full length AcP, AcPb or the combination of both. A control population was transduced with a CD25-expressing virus. Half the samples were stimulated with IL-1-beta for four hours, RNA was analyzed by microarray.
Publication Title
A central nervous system-restricted isoform of the interleukin-1 receptor accessory protein modulates neuronal responses to interleukin-1.
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Specimen part
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