Metformin reduces the incidence of cancer in diabetics or in animal models. At the cellular level, the effects of metformin include the inhibition of complex I of the mitochondrial electron transport chain, a reduction in ATP levels and the activation of the energy sensor AMP kinase. Metformin also prevents the production of reactive oxygen species in primary human cells expressing oncogenic ras and the DNA damage associated to the process.
Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-κB activation.
Sex, Specimen part, Treatment
View SamplesIslet amyloid polypeptide (IAPP) is the main component of amyloid deposits in type 2 diabetic patients. Cells overexpressing the human transcript of IAPP (hIAPP) present defects in insulin secretion.
Inhibition of BACE2 counteracts hIAPP-induced insulin secretory defects in pancreatic β-cells.
No sample metadata fields
View SamplesWith this study we wanted to evaluate the impact of murine norovirus infection of germfree mice and to compare it to germfree mice which have received fecal transplants of conventional mice. Overall design: whole small intestinal tissue analysis of 3 germfree, 3 germfree mice infected with murine norovirus and 3 conventionalized germfree mice
An enteric virus can replace the beneficial function of commensal bacteria.
No sample metadata fields
View SamplesNod2 has been extensively characterized as a bacterial sensor that induces an antimicrobial and inflammatory gene expression program. Therefore, it is unclear why Nod2 mutations that disrupt bacterial recognition are paradoxically among the highest risk factors for Crohns disease, which involves an exaggerated immune response directed at intestinal bacteria. Previous studies from our lab have shown that mice deficient in Atg16L1, another Crohns disease susceptibility gene, develop abnormalities in Paneth cells, specialized epithelial cells in the small intestine involved in antimicrobial responses.
Bacterial sensor Nod2 prevents inflammation of the small intestine by restricting the expansion of the commensal Bacteroides vulgatus.
Age, Specimen part
View SamplesTranscriptional profile of monocytes in the colon in response to C. rodentium infection Overall design: Eight samples have been analyzed. All are from Cd11b+Ly6C+ inflammatory monocytes sorted from colonic tissue 9 days after C. rodentium infection from Atg16L1HM(4) and WT(4) mice.
Autophagy proteins suppress protective type I interferon signalling in response to the murine gut microbiota.
Age, Specimen part, Subject
View SamplesFollowing skeletal muscle injury, muscle stem cells (satellite cells) are activated, proliferate, and differentiate to form myofibers. We show that mRNA decay protein AUF1 regulates satellite cell function through targeted degradation of specific mRNAs. AUF1 targets certain mRNAs containing 3 AU-rich elements (AREs) for rapid decay. Auf1-/- (KO) mice undergo accelerated skeletal muscle wasting with age and impaired muscle repair following injury. Satellite cell mRNA analysis and regeneration studies demonstrate that auf1-/- satellite cell self-renewal is impaired due to increased stability and overexpression of ARE-mRNAs. Control of ARE-mRNA decay by AUF1 and potentially other ARE-binding proteins represents a mechanism for adult stem cell regulation and is implicated in human muscle wasting diseases. We report the RNA transcript expression profiles from sorted satellite cells isolated from wild type (WT) and AUF1-null (KO) mice hindlimb muscles Overall design: Examination of RNA transcript expression from satellite cells of two genotypes Please note that mice are bred through a C57BL/6 strain of 129 background.
Targeted mRNA Decay by RNA Binding Protein AUF1 Regulates Adult Muscle Stem Cell Fate, Promoting Skeletal Muscle Integrity.
Age, Specimen part, Subject
View SamplesMethamphetamine (METH) is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge.
Methamphetamine preconditioning alters midbrain transcriptional responses to methamphetamine-induced injury in the rat striatum.
Sex, Age, Specimen part, Treatment
View SamplesWe performed the whole transcriptome analysis in Zscan4 positive ES cells (Em+) and Zscan4 negative ES cells (Em-) by using FACS-sorted MC1-ZE7 ES cells. Overall design: Whole RNA-seq in Zscan4 positive and negative cells
Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells.
No sample metadata fields
View SamplesSelf-renewal and pluripotency in human embryonic stem cells (hESCs) depends upon the function of a remarkably small number of master transcription factors (TFs) that include OCT4, SOX2, and NANOG. Endogenous factors that regulate and maintain the expression of master TFs in hESCs remain largely unknown and/or uncharacterized. We use a genome-wide, proteomics approach to identify proteins associated with the OCT4 enhancer. We identify known OCT4 regulators, plus a subset of potential regulators including a zinc finger protein, ZNF207, that plays diverse roles during development. In hESCs, ZNF207 partners with master pluripotency TFs to govern self-renewal and pluripotency while simultaneously controlling commitment of cells towards ectoderm through direct regulation of neuronal TFs, including OTX2. The distinct roles of ZNF207 during differentiation occur via isoform switching. Thus, a distinct isoform of ZNF207 functions in hESCs at the nexus that balances pluripotency and differentiation to ectoderm. Overall design: examine gene expression changes in ZNF207 knock down hESCs
A distinct isoform of ZNF207 controls self-renewal and pluripotency of human embryonic stem cells.
Specimen part, Subject
View SamplesCortical GABAergic interneurons constitute a highly diverse population of inhibitory neurons that are key regulators of cortical microcircuit function. An important and heterogeneous group of cortical interneurons specifically expresses the serotonin receptor 3A (5-HT3AR) but how this diversity emerges during development is poorly understood. Here we use single-cell transcriptomics to identify gene expression patterns operating in Htr3a-GFP+ interneurons during early steps of cortical circuit assembly. We identify 3 main molecular types of Htr3a-GFP+ interneurons, each displaying distinct developmental dynamics of gene expression. The transcription factor Meis2 is specifically enriched in a type of Htr3a-GFP+ interneurons spatially confined to the cortical white matter. These MEIS2 expressing interneurons appear to originate from a restricted region located at the embryonic pallial-subpallial boundary. Overall, this study identifies MEIS2 as a subclass-specific marker for 5-HT3AR-containing interstitial interneurons and demonstrates that the transcriptional and anatomical parcellation of cortical interneurons is developmentally coupled. Overall design: Single cell transcriptomics of cortical interneurons FACS sorted according to GFP-Htr3a+. Acquired from mouse brains of 3 different developmental ages: E18, P2, P5
Transcriptomic and anatomic parcellation of 5-HT<sub>3A</sub>R expressing cortical interneuron subtypes revealed by single-cell RNA sequencing.
Subject
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