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Rattus norvegicus
15 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The homeodomain transcription factor, Pdx-1, has important roles in pancreatic development and -cell function and survival. In the present study, we demonstrate that adenovirus-mediated overexpression of Pdx-1 in rat or human islets also stimulates cell replication. Moreover, co-overexpression of Pdx-1 with another homeodomain transcription factor, Nkx6.1, has an additive effect on proliferation compared to either factor alone, implying discrete activating mechanisms. Consistent with this, Nkx6.1 stimulates mainly -cell proliferation, whereas Pdx-1 stimulates both - and -cell proliferation. Furthermore, cyclins D1/D2 are upregulated by Pdx-1 but not by Nkx6.1, and inhibition of cdk4 blocks Pdx-1- but not Nkx6.1-stimulated islet cell proliferation. Genes regulated by Pdx-1 and not Nkx6.1 were identified by microarray analysis. Two members of the transient receptor potential cation (TRPC) channel family, TRPC3 and TRPC6, are upregulated by Pdx-1 overexpression, and siRNA-mediated knockdown of TRPC3/6 or TRPC6 alone inhibits Pdx-1-induced but not Nkx6.1-induced islet cell proliferation. Pdx-1 also stimulates ERK1/2 phosphorylation, an effect partially blocked by knockdown of TRPC3/6, and blockade of ERK1/2 activation with a MEK1/2 inhibitor partially impairs Pdx-1-stimulated proliferation. These studies define a pathway by which overexpression of Pdx-1 activates islet cell proliferation that is distinct from and additive to a pathway activated by Nkx6.1.
Publication Title
Pdx-1 activates islet α- and β-cell proliferation via a mechanism regulated by transient receptor potential cation channels 3 and 6 and extracellular signal-regulated kinases 1 and 2.
Sample Metadata Fields
Sex, Age, Specimen part
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GSE55079- Rattus norvegicus
- 36 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Loss of functional -cell mass is a hallmark of Type 1 and Type 2 diabetes, and methods for restoring these cells are needed. Nkx6.1 induces -cell proliferation, but the pathway by which Nkx6.1 activates -cell expansion has not been defined. Here we demonstrate that Nkx6.1 induces expression of the Nr4a1 and Nr4a3 orphan nuclear receptors, and that these factors are both necessary and sufficient for Nkx6.1-mediated -cell proliferation. Overexpression of the Nr4a receptors results in increased expression of key cell cycle inducers E2F1 and cyclin E1. Furthermore, Nr4a receptors induce components of the anaphase-promoting complex, including Ube2c.
Publication Title
Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Loss of functional -cell mass is a hallmark of Type 1 and Type 2 diabetes, and methods for restoring these cells are needed. We have previously reported that overexpression of the homeodomain transcription factor Nkx6.1 in rat pancreatic islets induces -cell proliferation and enhances glucose-stimulated insulin secretion, but the pathway by which Nkx6.1 activates -cell expansion has not been defined. Here we demonstrate that Nkx6.1 induces expression of the Nr4a1 and Nr4a3 orphan nuclear receptors, and that these factors are both necessary and sufficient for Nkx6.1-mediated -cell proliferation. Consistent with this finding, global knockout of Nr4a1 results in a decrease in -cell area in neonatal and young mice. Overexpression of Nkx6.1 and the Nr4a receptors results in increased expression of key cell cycle inducers E2F1 and cyclin E1. Furthermore, Nkx6.1 and Nr4a receptors induce components of the anaphase-promoting complex, including Ube2c, resulting in degradation of the cell cycle inhibitor p21CIP1. These studies identify a new bipartite pathway for activation of -cell proliferation, suggesting several new targets for expansion of functional -cell mass.
Publication Title
Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A major component of the cardiac stress response is the simultaneous activation of several gene regulatory networks. Interestingly, the transcriptional regulator steroid receptor coactivator-2, SRC-2 is often decreased during cardiac failure in humans. We postulated that SRC-2 suppression plays a mechanistic role in the stress response and that SRC-2 activity is an important regulator of the adult heart gene expression profile. Genome-wide microarray analysis, confirmed with targeted gene expression analyses revealed that genetic ablation of SRC-2 activates the fetal gene program in adult mice as manifested by shifts in expression of a) metabolic and b) sarcomeric genes, as well as associated modulating transcription factors. While these gene expression changes were not accompanied by changes in left ventricular weight or cardiac function, imposition of transverse aortic constriction (TAC) predisposed SRC-2 knockout (KO) mice to stress-induced cardiac dysfunction. In addition, SRC-2 KO mice lacked the normal ventricular hypertrophic response as indicated through heart weight, left ventricular wall thickness, and blunted molecular signaling known to activate hypertrophy. Our results indicate that SRC-2 is involved in maintenance of the steady-state adult heart transcriptional profile, with its ablation inducing transcriptional changes that mimic a stressed heart. These results further suggest that SRC-2 deletion interferes with the timing and integration needed to respond efficiently to stress through disruption of metabolic and sarcomeric gene expression and hypertrophic signaling, the three key stress responsive pathways.
Publication Title
SRC-2 coactivator deficiency decreases functional reserve in response to pressure overload of mouse heart.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
The heart requires a continuous supply of energy but has little capacity for energy storage and thus relies on exogenous metabolic sources. We previously showed that cardiac MED13 modulates systemic energy homeostasis in mice. Here we sought to define the extra-cardiac tissue(s) that respond to cardiac MED13 signaling. We show that cardiac over-expression of MED13 in transgenic (MED13cTg) mice confers a lean phenotype that is associated with increased lipid uptake, beta-oxidation and mitochondrial content in white adipose tissue (WAT) and liver. Cardiac expression of MED13 decreases metabolic gene expression and metabolite levels in heart and liver but enhances them in WAT. Although exhibiting increased energy expenditure in the fed state, MED13cTg mice metabolically adapt to fasting. Furthermore, MED13cTg hearts oxidize fuel that is readily available, rendering them more efficient in the fed state. Parabiosis experiments in which circulations of wild-type and MED13cTg mice are joined, reveal that circulating factor(s) in MED13cTg mice promote enhanced metabolism and leanness. These findings demonstrate that MED13 acts within the heart to promote systemic energy expenditure in extra-cardiac energy depots and point to an unexplored metabolic communication system between the heart and other tissues. Overall design: n=3 for each genotype and organ
Publication Title
MED13-dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
SIRT3 is a mitochondrial NAD(+)-dependent protein deacetylase, which regulates the enzymatic activity of several mitochondrial proteins.
Publication Title
SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice there is an influx of tumor macrophages that polarize towards wound repair and immune suppression.
Publication Title
Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Drosophila melanogaster
- 32 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
To gain insight into the molecular underpinnings of the post-mating response that depend on the germline, we independently assess the contribution of the female germline and the male germline on gene expression changes in head tissues of females using RNA-seq. Overall design: mRNA profiles of head tissues in virgin and mated (1 and 3 days post-mating) females that either have or are lacking a germline and females mated to males that either have or are lacking a germline. Samples were generated in triplicate and sequenced on an Illumina Genome Analyzer IIx.
Publication Title
The <i>Drosophila</i> Post-mating Response: Gene Expression and Behavioral Changes Reveal Perdurance and Variation in Cross-Tissue Interactions.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Blood-stage malaria initiates both innate and adaptive immune responses, inclusive a strong activation of the mononuclear phagocyte network. Here we show that Plasmodium infection results in a transient loss of embryonically established tissue-resident macrophages in spleen, liver and lungs, much before the peak of parasitemia. During acute blood-stage malaria, fate mapping analysis revealed that inflammatory monocytes contribute to the repopulation of the emptied niches of splenic red pulp macrophages and hepatic Kupffer cells, while lung alveolar macrophages refill their niche mainly through self-renewal. Interestingly, the local microenvironment of spleen and liver can “imprint” the molecular characteristics of fetal-derived macrophages in new immigrants from bone marrow including almost identical gene expression profiles and turnover kinetics. Overall design: Mice were infected with parasitized P. yoelii erythrocytes. Organ samples were collected in triplicates from uninfected mice and from mice infected 35 days before and after parasite clearance.
Publication Title
Organ-Specific Fate, Recruitment, and Refilling Dynamics of Tissue-Resident Macrophages during Blood-Stage Malaria.
Sample Metadata Fields
Specimen part, Subject
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