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Mus musculus
14 Downloadable Samples
Description
Fast-spiking (FS) interneurons are important elements of neocortical circuitry that constitute the primary source of synaptic inhibition in adult cortex and impart temporal organization on ongoing cortical activity. The highly specialized intrinsic membrane and firing properties that allow cortical FS interneurons to perform these functions are attributable to equally specialized gene expression, which is ultimately coordinated by cell-type-specific transcriptional regulation. Although embryonic transcriptional events govern the initial steps of cell-type specification in most cortical interneurons, including FS cells, the electrophysiological properties that distinguish adult cortical cell types emerge relatively late in postnatal development, and the transcriptional events that drive this maturational process are not known. To address this, we used mouse whole-genome microarrays and whole-cell patch clamp to characterize the transcriptional and electrophysiological maturation of cortical FS interneurons between postnatal day 7 (P7) and P40. We found that the intrinsic and synaptic physiology of FS cells undergoes profound regulation over the first 4 postnatal weeks and that these changes are correlated with primarily monotonic but bidirectional transcriptional regulation of thousands of genes belonging to multiple functional classes. Using our microarray screen as a guide, we discovered that upregulation of two-pore K leak channels between P10 and P25 contributes to one of the major differences between the intrinsic membrane properties of immature and adult FS cells and found a number of other candidate genes that likely confer cell-type specificity on mature FS cells.
Publication Title
Transcriptional and electrophysiological maturation of neocortical fast-spiking GABAergic interneurons.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Most tumors are epithelial-derived, and although disruption of polarity and aberrant cellular junction formation is a poor prognosticator in human cancer, the role of polarity determinants in oncogenesis is poorly understood. Using in vivo selection, we identified a mammalian orthologue of the Drosophila polarity regulator crumbs as a gene whose loss of expression promotes tumor progression. Immortal baby mouse kidney epithelial (iBMK) cells selected in vivo to acquire tumorigenicity displayed dramatic repression of crumbs3 (crb3) expression associated with disruption of tight junction formation, apicobasal polarity, and contact-inhibited growth. Restoration of crb3 expression restored junctions, polarity and contact inhibition, while suppressing migration and metastasis. These findings suggest a role for mammalian polarity determinants in suppressing tumorigenesis that may be analogous to the well-studied polarity tumor suppressor mechanisms in Drosophila.
Publication Title
Role of the polarity determinant crumbs in suppressing mammalian epithelial tumor progression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
Description
Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons.
Publication Title
Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Rattus norvegicus
- 6 Downloadable Samples
Description
A series contains a set of transcript intensity values measured by Affymetrix microarray.
Publication Title
Systems-level analysis of cell-specific AQP2 gene expression in renal collecting duct.
Sample Metadata Fields
Sex, Specimen part
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GSE13667- Mus musculus
- 6 Downloadable Samples
Description
This series of microarray data contain transcript intensity of mpkCCD cells.
Publication Title
Systems-level analysis of cell-specific AQP2 gene expression in renal collecting duct.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
Description
We demonstrate that expression of key markers of keratinocyte differentiation is suppressed by exposure to sodium arsenite. Folate deficiency exacerbates this effect. In addition, cancer-related cell movement genes, and growth and proliferation genes are altered. Several redox-sensitive transcription factors are implicated in mediating these gene expression changes due to arsenic treatment and folate deficiency.
Publication Title
Folate deficiency enhances arsenic effects on expression of genes involved in epidermal differentiation in transgenic K6/ODC mouse skin.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
Description
Primordial genomic challenge compromises embryonic development and survival, and surveillance of deployed transcriptional programs may provide an early opportunity to forecast phenotype abnormalities. Here, comparisons between wild-type and calreticulin-ablated embryonic stem cells revealed transcriptome shifts precipitated by calreticulin loss. Bioinformatic analysis identified down and up-regulation in 1187 and 418 genes, respectively. Cardiovascular development precedes other organogenic programs, and examination of cardiogenic genes revealed a map of calreticulin-calibrated expression profiles that encompass the developmental regulators, Ccnd1, Ccnd2 and Notch1. Interrogation of primary function in the resolved network forecasted abnormalities during myocardial development. Whole embryo magnetic resonance imaging, verified by pathoanatomical analysis, diagnosed prominent ventricular septal defect. Correlation clustering and network resolution of probesets associated with protein folding/chaperoning and calcium handling demonstrated 14 and 19 genes, respectively, modulated by calreticulin deficiency. Calreticulin deletion provoked ontological re-prioritization of gene expression, molecular transport and protein trafficking that translated into multiple subcellular functional outcomes. Individual stem cell-derived cardiomyocytes lacking calreticulin demonstrated a disorganized contractile apparatus with mitochondrial paucity and architectural aberrations. Thus, bioinformatic deconvolution of primordial embryonic stem cell transcriptomes enables predictive phenotyping of defective developmental networks that coalesce from complex systems biology hierarchies.
Publication Title
Decoded calreticulin-deficient embryonic stem cell transcriptome resolves latent cardiophenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
We used gene expression microarrays to identify genes whose expression was influenced differently by TNFa in Fancc-deficient mice compared to wild type (WT) mice. To identify genes whose expression was directly or indirectly influenced by Fancc, we looked in particular for genes either suppressed or induced by TNF in WT cells that were not affected by TNF in Fancc-deficient cells.
Publication Title
FANCL ubiquitinates β-catenin and enhances its nuclear function.
Sample Metadata Fields
Specimen part
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
- 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