High-throughput gene expression profiling has become an important tool for investigating transcriptional activity in a variety of biological samples. To date, the vast majority of these experiments have focused on specific biological processes and perturbations. Here, we profiled gene expression from a diverse array of normal tissues, organs, and cell lines in mice. Keywords: multiple tissues
Expression analysis of G Protein-Coupled Receptors in mouse macrophages.
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View SamplesRegeneration of differentiated tissue in mammals is rare. In an effort to identify genes that affect the healing process, we screened G3 mice containing germline point mutations for closure of an ear punch wound. One particular line was identified with a heritable hole closure phenotype containing differentiated tissue. Mapping and sequencing efforts revealed that the mutant mice harbor a R244Q point mutation coded by the TGFBR1 gene which leads to enhanced signaling activity in a reporter gene assay. Although there was no obvious effect on the immune system, bone marrow stromal cells from the mutant mice revealed accelerated chondrogenesis, mimicking the in vivo development of cartilage islands in the regenerated ears. This genetically well-defined mouse model should help to further dissect the role of TGF-beta signaling in vertebrate healing and regeneration.
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View SamplesNew insulin-producing pancreatic beta-cells are formed primarily by self-replication during adult life. To identify small molecules that can induce beta cell replication, a large chemical library was screened for proliferation of growth-arrested, reversibly immortalized mouse beta-cells using an automated high-throughput screening platform. A number of structurally diverse, active compounds were identified including phorbol esters, which likely act through protein kinase C, and a group of thiophene-pyrimidines that stimulate beta-cell proliferation by activating the Wnt signaling pathway. A group of dihydropyridine (DHP) derivatives was also shown to reversibly induce beta-cell replication in vitro by activating L-type calcium channels (LTCCs). Our data indicate that the LTCC agonist 2a affects the expression of genes involved in cell cycle progression and cellular proliferation. Furthermore, treatment of beta-cells with both LTCC agonist 2a and the Glp-1 receptor agonist Ex-4 showed an additive effect on beta-cell replication. The identification of small molecules that induce beta-cell proliferation suggests that it may be possible to reversibly expand other quiescent cells to overcome deficits associated with degenerative and/or autoimmune diseases.
Identification of small-molecule inducers of pancreatic beta-cell expansion.
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View SamplesIncreasing evidence suggests that Long non-coding RNAs (LncRNAs) represent a new class of regulators of stem cells. However, the roles of LncRNAs in stem cell maintenance and myogenesis remain largely unexamined. For this study, hundreds of novel intergenic LncRNAs were identified that are expressed in myoblasts and regulated during differentiation. One of these LncRNAs, termed LncMyoD, is encoded next to the Myod gene and is directly activated by MyoD during myoblast differentiation. Knockdown of LncMyoD strongly inhibits terminal muscle differentiation largely due to a failure to exit the cell cycle. LncMyoD directly binds to IGF2-mRNA-binding-protein 2 (IMP2) and negatively regulates IMP2-mediated translation of proliferation genes such as N-Ras and c-Myc. While the RNA sequence of LncMyoD is not well-conserved between human and mouse, its locus, gene structure and function is preserved. The MyoD-LncMyoD-IMP2 pathway elucidates a mechanism as to how MyoD blocks proliferation to create a permissive state for differentiation.
A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation.
Age
View SamplesThe mitochondrial superoxide dismutase (SOD2) is a major antioxidant protein which detoxifies superoxide anion radicals generated by mitochondrial respiration (Weisiger and Fridovich, J. Biol. Chem. 1973). We designed a model of oxidative stress-induced anemia caused by SOD2-deficiency (Friedman et al. J. Exp. Med. 2001). Our previous work showed that mice reconstituted with SOD2-deficient hematopoietic stem cells develop an anemia with striking similarity to human sideroblastic anemia (SA) (Friedman et al. Blood 2004; Martin et al. Exp Hematol 2005). Our overall goal was to define early events in the pathogenesis of SOD2-deficiency SA and, in particular, to identify genes involved in the response of erythroid progenitors to oxidative stress. We compared gene expression of sorted TER-119+ CD71+ erythroblasts from SOD2-/- ('KO') versus Sod2+/+ ('WT') hematopoietic stem cell recipients using cDNA microarrays.
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View SamplesTo identify targets of PDGFRb signaling and potentially new markers for pericyte activation, we used microarray analysis to compare gene expression in control and mutant pericytes expressing a constitutively active PDGFRb.
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Specimen part
View SamplesMerm1/Wbscr22 is one of genes in chromosomal region deleted in Williams-Beuren syndrome, a multisystem developmental disorder. Wbscr22 contains a nuclear localization signal and an S-adenosyl-L-methionine-dependent methyltransferase fold, but its real function is completely unknown.In this study, to examine the function, we compared the gene expression profiles between control and Merm1/Wbscr22 knock-downed tumor cells.
The novel metastasis promoter Merm1/Wbscr22 enhances tumor cell survival in the vasculature by suppressing Zac1/p53-dependent apoptosis.
Cell line, Treatment
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Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Age, Specimen part, Treatment, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sex, Specimen part, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
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Sex, Specimen part
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