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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.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
Description
Glomerular RNA comparison between wild-type and podocyte specific deletion of the PTIP gene in 1 month old kidneys. The PTIP gene was deleted using a floxed allele and a Podocin-Cre driver strain.
Publication Title
Altering a histone H3K4 methylation pathway in glomerular podocytes promotes a chronic disease phenotype.
Sample Metadata Fields
Specimen part
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GSE13364- Mus musculus
- 6 Downloadable Samples
Description
Microarray analysis was performed on BWF1 mice spleenocyte cells in control and pCONS treated mice.
Publication Title
Distinct gene signature revealed in white blood cells, CD4(+) and CD8(+) T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
Description
Analysis of gene expression in lungs of C57BL/6J mice that develop chronic airway disease phenotypes after a single Sendai virus infection, compared with mice treated with UV-inactivated virus.
Publication Title
Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease.
Sample Metadata Fields
Sex, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Journal : Blood. 2009 Jul 9;114(2):469-77. Epub 2009 May 13.
Publication Title
Endothelial deletion of hypoxia-inducible factor-2alpha (HIF-2alpha) alters vascular function and tumor angiogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Group-2 innate lymphoid cells (ILC2) serve crucial function in allergy and asthma. Activated ILC2 rapidly proliferate and secret large amounts of type-2 cytokines, such as IL-5 and IL-13. Mechanisms underlying still remain ambiguous. Here we report that Myc is required for ILC2 proliferation and activation in allergic airway inflammation. Inhibition of Myc impair the ILC2 proliferation in vivo and prevented ILC2-mediated airway hyperresponsiveness in vivo.
Publication Title
A critical role for c-Myc in group 2 innate lymphoid cell activation.
Sample Metadata Fields
Genotype, Cell line
View Samples- Mus musculus
- 30 Downloadable Samples
Description
Murine models have been valuable instruments in defining the pathogenesis of diabetic nephropathy (DN), but they only partially recapitulate disease manifestations of human DN, limiting their utility . In order to define the molecular similarities and differences between human and murine DN, we performed a cross-species comparison of glomerular transcriptional networks. Glomerular gene expression was profiled in patients with early type 2 DN and in three mouse models (streptozotocin DBA/2 mice, db/db C57BLKS, and eNOS-deficient C57BLKS db/db mice). Species-specific transcriptional networks were generated and compared with a novel network-matching algorithm. Three shared, human-mouse cross-species glomerular transcriptional networks containing 143 (Human-STZ), 97 (Human- db/db), and 162 (Human- eNOS-/- db/db) gene nodes were generated. Shared nodes across all networks reflected established pathogenic mechanisms of diabetic complications, such as elements of JAK-STAT and VEGFR signaling pathways . In addition, novel pathways not formally associated with DN and cross-species gene nodes and pathways unique to each of the human-mouse networks were discovered. The human-mouse shared glomerular transcriptional networks will assist DN researchers in the selection of mouse models most relevant to the human disease process of interest. Moreover, they will allow identification of new pathways shared between mice and humans.
Publication Title
Identification of cross-species shared transcriptional networks of diabetic nephropathy in human and mouse glomeruli.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 14 Downloadable Samples
Description
Recurrent somatic mutations in TET2 and in other genes that regulate the epigenetic state have been identified in patients with myeloid malignancies and in other cancers. However, the in vivo effects of Tet2 loss have not been delineated. We report here that Tet2 loss leads to increased stem-cell self-renewal and to progressive stem cell expansion. Consistent with human mutational data, Tet2 loss leads to myeloproliferation in vivo, notable for splenomegaly and monocytic proliferation. In addition, haploinsufficiency for Tet2 confers increased self-renewal and myeloproliferation, suggesting that the monoallelic TET2 mutations found in most TET2-mutant leukemia patients contribute to myeloid transformation. This work demonstrates that absent or reduced Tet2 function leads to enhanced stem cell function in vivo and to myeloid transformation.
Publication Title
Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Formation of the complex vertebrate nervous system begins when pluripotent cells of the early embryo are directed to acquire a neural fate. Although cell intrinsic controls play an important role in this process, the molecular nature of this regulation is not well defined. Here we assessed the role for Geminin, a nuclear protein expressed in embryonic cells, in neural fate acquisition from mouse embryonic stem (ES) cells. While Geminin knockdown does not affect the ability of ES cells to maintain or exit pluripotency, we found that it significantly impairs their ability to acquire a neural fate. Conversely, Geminin overexpression promotes neural gene expression, even in the presence of growth factor signaling that antagonizes neural transcriptional responses. These data demonstrate that Geminins activity contributes to mammalian neural cell fate acquisition. We investigated the mechanistic basis of this phenomenon and found that Geminin maintains a hyperacetylated and open chromatin conformation at neural genes. Interestingly, recombinant Geminin protein also rapidly alters chromatin acetylation and accessibility even when Geminin is combined with nuclear extract and chromatin in vitro. These findings define a novel activity for Geminin in regulation of chromatin structure. Together, these data support a role for Geminin as a cell intrinsic regulator of neural fate acquisition that promotes expression of neural genes by regulating chromatin accessibility and histone acetylation.
Publication Title
Geminin promotes neural fate acquisition of embryonic stem cells by maintaining chromatin in an accessible and hyperacetylated state.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
Description
The aim of the study was to illucidate how BAFF mediates B cell survival and growth through the identification of BAFF-regulated genes.
Publication Title
BAFF controls B cell metabolic fitness through a PKC beta- and Akt-dependent mechanism.
Sample Metadata Fields
No sample metadata fields
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