Filters
Technology
Platform
Mus musculus
8 Downloadable Samples
Description
Ethanol inhibits the proliferation of neural stem cells in the fetal, adolescent, and adult brain. The consequences are cognitive deficits associated with fetal alcohol spectrum disorder and alcohol use disorder. We tested the hypothesis that ethanol affects progression through cell cycle checkpoints by differentially modifying transcriptional processes. Monolayer cultures of NS-5 neural stem cells were treated for 48 hr with the mitogenic agent FGF2 or the anti-mitogenic TGF1 in the absence or presence of ethanol. Cell cycle elongation was induced by a global down-regulation of genes involved in cell cycle progression, including the cyclin E system. Checkpoint regulation occurred downstream of p21 and Jun-oncogene signaling cascades. Thus, ethanol can affect cell cycle progression by altering transcript expression of strategic genes downstream of the G1/S checkpoint.
Publication Title
Ethanol-induced methylation of cell cycle genes in neural stem cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
Description
Signaling by the cytokine LIF and its downstream transcription factor, STAT3, prevents differentiation of pluripotent embryonic stem cells (ESCs) by opposing MAP kinase signaling. This contrasts with most cell types where STAT3 signaling induces differentiation. We find that STAT3 binding across the pluripotent genome is dependent upon Brg, the ATPase subunit of a specialized chromatin remodeling complex (esBAF) found in ESCs. Brg is required to establish chromatin accessibility at STAT3 binding targets, in essence preparing these sites to respond to LIF signaling. Moreover, Brg deletion leads to rapid Polycomb (PcG) binding and H3K27me3-mediated silencing of many Brg-activated targets genome-wide, including the target genes of the LIF signaling pathway. Hence, one crucial role of Brg in ESCs involves its ability to potentiate LIF signaling by opposing PcG. Contrary to expectations, Brg also facilitates PcG function at classical PcG target including all four Hox loci, reinforcing their repression in ESCs. These findings reveal that esBAF does not simply antagonize PcG, but rather, the two chromatin regulators act both antagonistically and synergistically with the common goal of supporting pluripotency.
Publication Title
esBAF facilitates pluripotency by conditioning the genome for LIF/STAT3 signalling and by regulating polycomb function.
Sample Metadata Fields
Cell line, Treatment
View Samples- 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
- 12 Downloadable Samples
Description
Cardiac disease accounts for the largest proportion of adult mortality and morbidity in the industrialized world. However, progress toward improved clinical treatments is hampered by an incomplete understanding of the genetic programs controlling early cardiogenesis. To better understand this process, we set out to identify genes whose expression is enriched within early cardiac fated populations, obtaining the transcriptional signatures of mouse embryonic stem cells (mESCs) differentiating along a cardiac path.
Publication Title
Efficient array-based identification of novel cardiac genes through differentiation of mouse ESCs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
Description
Mouse embryonic stem cells can differentiate in vitro into spontaneously contracting cardiomyocytes. The main objective of this study was to investigate cardiogenesis in cultures of differentiating embryonic stem cells (ESCs) and to determine how closely it mimics in vivo cardiac development. We identified and isolated a population of cardiac progenitor cells (CPCs) through the use of a reporter DNA construct that allowed the expression of a selectable marker under the control of the Nkx2.5 enhancer. We proceeded to characterize these CPCs by examining their capacity to differentiate into cardiomyocytes and to proliferate. We then performed a large-scale temporal microarray expression analysis in order to identify genes that are uniquely upregulated or downregulated in the CPC population. We determined that the transcriptional profile of the mESC derived CPCs was consistent with pathways known to be active during embryonic cardiac development. We conclude that in vitro differentiation of mESCs recapitulates the early steps of mouse cardiac development.
Publication Title
Mouse ES cell-derived cardiac precursor cells are multipotent and facilitate identification of novel cardiac genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Ocular immune privilege (IP) limits immune surveillance of intraocular tumors as certain immunogenic tumor cell lines (P815, E.G7-OVA) that are rejected when transplanted in the skin grow progressively when placed in the anterior chamber (a.c.) of the eye. As splenectomy (SPLNX) is known to terminate ocular IP, we characterized immune mechanisms responsible for spontaneous rejection of intraocular tumors in SPLNX mice as a first step toward identifying how to restore tumoricidal activity within the eye. Microarray data showed a 3-fold increase in interferon (IFN)- and a 2.7-fold increase in Fas ligand (FasL). There was a robust increase in transcripts (127 of 408 surveyed) from interferon (IFN)-stimulated genes and a marked decrease (in 40 of 192 surveyed) in the expression of cell-cycle-associated genes. Non-microarray data confirmed that IFN, FasL and CD8+ T cells but not perforin or TNF were required for elimination of intraocular E.G7-OVA tumors that culminated in destruction of the eye (ocular phthsis). IFN and FasL did not target tumor cells directly as the majority of SPLNX IFNR1-/- mice and Fas-defective lpr mice failed to eliminate ocular E.G7-OVA tumors that expressed Fas and IFNR1. Bone marrow chimeras showed that immune cell expression of IFNR1 and Fas was critical and that SPLNX increased the frequency of activated macrophages within ocular tumors in an IFN- and Fas/FasL-dependent manner. Rejection of intraocular tumors was associated with increased ocular mRNA expression of several inflammatory genes including FasL, NOS2, CXCL2 and T-bet. Our data support a model in which IFN- and Fas/FasL-dependent activation of intratumoral macrophage by CD8+ T cells promotes severe intraocular inflammation that indirectly eliminates intraocular tumors by inducing phthisis. The immunosuppressive mechanisms which maintain ocular IP likely interfere with the interaction between CD8+ T cells and macrophage to limit immunosurveillance of intraocular tumors.
Publication Title
Splenectomy promotes indirect elimination of intraocular tumors by CD8+ T cells that is associated with IFNγ- and Fas/FasL-dependent activation of intratumoral macrophages.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 57 Downloadable Samples
Description
In order to understand how biochemical and genetic differences correlate with treatment response, we measured depressive-like behavior, gene expression and the levels of thirty-six neurobiochemical analytes across a panel of genetically-diverse mouse inbred lines after chronic treatment with vehicle or fluoxetine. Neurobiochemical markers were chosen based on their putative molecular function within pathways proposed to underlie depression, which include neuronal transmission, HPA-axis regulation, and neuroimmune processes. The goal of this study is to establish genetic and biochemical biomarkers that can predict treatment response and to propose a molecular pathway that is critical in mediating anti-depressant response.
Publication Title
Evaluating genetic markers and neurobiochemical analytes for fluoxetine response using a panel of mouse inbred strains.
Sample Metadata Fields
Sex, 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
View Samples
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
- 10 Downloadable Samples
Description
Gene expression profile of joint tissue from C3H and interval specific congenic mouse lines (ISCL) following infection with Borrelia burgdorferi
Publication Title
Interval-specific congenic lines reveal quantitative trait Loci with penetrant lyme arthritis phenotypes on chromosomes 5, 11, and 12.
Sample Metadata Fields
Specimen part
View Samples