To investigate the importance of STAT3 in the establishment of ES cells we have in a first step derived stable pluripotent embryonic stem cells from transgenic FVB mice expressing a conditional tamoxifen dependent STAT3-MER fusion protein. In a second step, STAT3-MER overexpressing cells were used to identify STAT3 pathway-related genes by expression profiling in order to identify new key-players involved in maintenance of pluripotency in ES cells.
Expression profiling in transgenic FVB/N embryonic stem cells overexpressing STAT3.
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View SamplesControlled decay of cytokine and chemokine mRNAs restrains the time and amplitude of inflammatory responses. Tristetraprolin (TTP) binds to AU-rich elements in 3 untranslated regions of mRNA and targets the bound mRNA for degradation. We have addressed here the function of TTP in balancing the macrophage activation state by a comprehensive analysis of TTP-dependent mRNA decay in LPS-stimulated macrophages from WT and TTP-deficient mice.
Tristetraprolin-driven regulatory circuit controls quality and timing of mRNA decay in inflammation.
Specimen part
View SamplesTranscriptional and posttranscriptional regulatory networks play a crucial role in the maintenance and adaptation of pancreatic beta-cell function. In this study we show that the levels of the prototypic neuroendocrine miRNA-7 are regulated in islets of obese, diabetic and aged mouse models. Using gain- and loss-of-function models we demonstrate that miR-7 regulates crucial members of the endocrine pancreatic transcriptional network controlling differentiation and insulin synthesis. Importantly, it also directly regulates key proteins in the insulin granule secretory machinery. These results reveal an interconnecting miR-7 genomic circuit that influences beta-cell differentiation, insulin synthesis and release and define a role for miR-7 as an endocrine checkpoint to stabilize beta-cell function during metabolic stress. These findings have implications for miR-7 inhibitors as potential therapies for type 2 diabetes and neurodegenerative diseases.
MicroRNA-7a regulates pancreatic β cell function.
Specimen part, Cell line, Treatment
View SamplesAbhd15 is mainly expressed in white adipose tissues and highly upregulated upon adipogenesis. Abhd15 expression is correlated with insulin resistance in obese humans, however its physiological function remains unknown. We used the microarray technology to gain insight into ABHD15s physiological function by identifying dysregulated genes in eWAT from Abhd15-ko mice in comparison to WT mice.
Loss of ABHD15 Impairs the Anti-lipolytic Action of Insulin by Altering PDE3B Stability and Contributes to Insulin Resistance.
Sex, Specimen part
View SamplesThe transcription factor STAT1 is essential for interferon- (IFN) mediated protective immunity in humans and mice. Two splice isoforms of STAT1, STAT1 and STAT1, differ with regard to a C-terminal transactivation domain, which is absent in STAT1. Dimers of STAT1 are therefore considered transcriptionally inactive and potential competitive inhibitors of STAT1. Contrasting this view, generation and analysis of mice deficient for either STAT1 or STAT1 demonstrated transcriptional activity of the STAT1 isoform and its enhancement of innate immunity. Gene expression profiling in primary cells revealed overlapping, but also non-redundant and gene-specific activities of STAT1 and STAT1 in response to IFN. Consistently, both isoforms mediated protective, IFN-dependent immunity against the bacterium Listeria monocytogenes, although with remarkably different efficiency. In contrast, STAT1 and STAT1 were largely redundant for transcriptional responses to IFN/ and for IFN/-dependent antiviral activity. Collectively, our data shed new light on how STAT1 isoforms contribute to antimicrobial immunity.
STAT1β is not dominant negative and is capable of contributing to gamma interferon-dependent innate immunity.
Specimen part
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