Adult zebrafish can completely regenerate their caudal fin following amputation. This complex process is initiated by the formation of an epithelial would cap over the amputation site by 12 hours post amputation (hpa). Once the cap is formed, mesenchymal cells proliferate and migrate from sites distal to the wound plane and accumulate under the epithelial cap forming the blastemal structure within 48 hpa. Blastemal cells proliferate and differentiate, replacing the amputated tissues, which are populated with angiogenic vessels and innervating nerves during the regenerative outgrowth phase which is completed around 14 days post amputation (dpa). Regenerative outgrowth does not occur in TCDD-exposed zebrafish. To identify the molecular pathways that are perturbed by TCDD exposure, male zebrafish were i.p. injected with 50 ng/g TCDD or vehicle and caudal fins were amputated. Regenerating fin tissue was collected at 1, 3 and 5 dpa for mRNA abundance analysis. Microarray analysis and quantitative real time PCR revealed that wound healing and regeneration alone altered the expression of nearly 900 genes by at least two fold between 1 and 5 dpa. TCDD altered the abundance of 370 genes at least two fold. Among these, several known aryl hydrocarbon responsive genes were identified in addition to several genes involved in extracellular matrix composition and metabolism. The profile of misexpressed genes is suggestive of impaired cellular differentiation and extracellular matrix composition potentially regulated by Sox9b.
Regenerative growth is impacted by TCDD: gene expression analysis reveals extracellular matrix modulation.
Sex, Time
View SamplesPlasma cell differentiation involves coordinated changes in gene expression and functional properties of B cells. Here, we study the role of Mzb1, a Grp94 co-chaperone that is expressed in marginal zone (MZ) B cells and during the terminal differentiation of B cells to antibody-secreting cells (ASCs). By analyzing Mzb1 -/- Prdm1 +/gfp mice, we find that Mzb1 is specifically required for the differentiation and function of ASCs in a T cell-independent immune response. We find that Mzb1-deficiency mimics, in part, the phenotype of Blimp1 deficiency, including the impaired secretion of IgM and the deregulation of Blimp1 target genes. In addition, we find that Mzb1 -/- plasmablasts show a reduced activation of b1 integrin, which contributes to the impaired plasmablast differentiation and migration of ASCs to the bone marrow. Thus, Mzb1 function is required for multiple aspects of plasma cell differentiation. Overall design: Splenic B cells were purified from Mzb1 +/+ Prdm1 +/gfp and Mzb1 -/- Prdm1 +/gfp mice using anti-B220 magnetic beads and cultured in the presence of 25ug/ml LPS. After 4 days, undifferentiated CD138 - Blimp - B cell blasts (Activated B Cells), CD138 - Blimp + (Pre-PB cells), and CD138 + Blimp + (PB cells) were isolated with FACSAria (Becton Dickinson) sort.
Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell differentiation and β1-integrin function.
Specimen part, Cell line, Subject
View SamplesWe generated Gadd45a,b,g triple-knockout mouse embryonic stem cells and performed RNA-seq expression profiling under six different conditions of cell culture and in vitro differentiation. Overall design: Gadd45a,b,g triple knockout (TKO) mouse embryonic stem cells (mESC) were generated by CRISPR/Cas9. RNA-Seq was performed to compare the transcriptome in three independent Gadd45 TKO versus three independent control mESC lines under different conditions: (i) Serum cultured mESC, (ii) Vitamin C treated mESC, (iii) 2i treated mESC, (iv) mESC differentiated as embryoid bodies (EB), (v) mESC differentiated as a serum-free monolayer, and (vi) EB stimulated with retinoic acid (RA).
GADD45 promotes locus-specific DNA demethylation and 2C cycling in embryonic stem cells.
Specimen part, Cell line, Subject
View SamplesExposures to dioxin, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause a wide array of toxicities in vertebrates and is mostly considered to be mediated through the inappropriate activation of the aryl hydrocarbon receptor (Ahr) signaling pathway. Although transcriptional regulation by Ahr is widely studied, the molecular mechanisms responsible for the adverse outcomes after Ahr activation are largely unknown. To identify the important events downstream of AHR activation that play an actual role in the toxic responses, we employed the zebrafish caudal fin regeneration models since Ahr activation blocks the regenerative process. Zebrafish regenerate their caudal fins by an orchestrated progression of cell migration, differentiation and proliferation controlled by a multitude of signaling pathways. This complex process was exploited as an in vivo platform to identify cross talk between Ahr and other signaling pathways. Global genomic analysis was performed in the larval regenerating fin tissue after exposure to TCDD in order to identify genes differentially regulated after Ahr activation. Comparative toxicogenomic analysis revealed that both adult and larval fins respond to TCDD during regeneration with mis-expression of Wnt signaling pathway members and Wnt target genes.
Crosstalk between AHR and Wnt signaling through R-Spondin1 impairs tissue regeneration in zebrafish.
No sample metadata fields
View SamplesMacrophages phagocytose bacteria. Certain pathogenic bacteria access and replicate within the cytosol of infected macrophages and induce changes in macrophage gene expression by triggering of innate immune receptors and/or the effects of bacterial virulence factors. We used microarray analysis to identify changes in macrophage gene expression following infection with Listeria monocytogenes.
Induction of IFN-alphabeta enables Listeria monocytogenes to suppress macrophage activation by IFN-gamma.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic Fatty liver disease.
Age, Specimen part, Disease
View SamplesLiver global gene expression patterns of 9 GNMT-knockout mice histopathologically determined to have non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) together with 10 MAT1A-knockout mice histopathologically determined to have steatosis and NASH. All these have their respective wild type patterns. These were analyzed to define signatures to study the pathogenesis of NAFLD-derived HCC, explore which subtypes of cancers can be investigated using mouse models and define a signature of HCC differential survival that can be used to characterize HCC subtypes of different survival derived from mixed etiologies.
Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic Fatty liver disease.
Age, Specimen part, Disease
View SamplesWe hypothesize that germline variation influences susceptibility to aggressive prostate tumor
GNL3 and SKA3 are novel prostate cancer metastasis susceptibility genes.
Specimen part
View SamplesZebrafish have the remarkable ability to regenerate body parts including the heart, spinal cord and fins by a process referred to as epimorphic regeneration. Recent studies have illustrated that similar to adult zebrafish, early life stage-larvae also possess the ability to regenerate the caudal fin. A comparative genomic analysis was used to determine the degree of conservation in gene expression among the regenerating adult caudal fin, adult heart and larval fin. Results indicate that these tissues respond to amputation/injury with strikingly similar genomic responses. Comparative analysis revealed raldh2, a rate-limiting enzyme for the synthesis of Retinoic acid (RA), as one of the highly induced genes across the three regeneration platforms.
Comparative expression profiling reveals an essential role for raldh2 in epimorphic regeneration.
No sample metadata fields
View SamplesGlobal gene expression patterns of 2 human steatosis and 9 human non-alcoholic steatohepatitis (NASH) together with their respective control patterns were analyzed to define the non-alcoholic fatty liver disease (NAFLD) progression molecular characteristics and to define NASH early markers from steatosis.
Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic Fatty liver disease.
Specimen part, Disease
View Samples