This SuperSeries is composed of the SubSeries listed below.
NF-κB inhibition rescues cardiac function by remodeling calcium genes in a Duchenne muscular dystrophy model.
Age
View SamplesWe found genetic deletion of IKK in mdx cardiomyocytes improved cardiac function and normalized calcium transients. We used microarrays to profile gene expression in hearts of mdx mice with intact IKK signaling and hearts of mdx mice with IKK-deficient cardiomyocytes to identify genes differentially regulated by NF-[kappa]B. signaling in dystrophic hearts.
NF-κB inhibition rescues cardiac function by remodeling calcium genes in a Duchenne muscular dystrophy model.
Age
View SamplesExpression profiling of mRNA abundance in the adult mouse olfactory epithelium during replacement of OSNs forced by the bilateral ablation of the olfactory bulbs. The experiment was done on 6 week old male C57Bl/6 mice. Olfactory epithelium tissue samples were collected on days 1, 5, and 7 after bulbectomy. The cellular processes activated by bulbectomy include apoptosis of mature olfactory sensory neurons, infiltration of macrophages and dendritic cells, stimulation of proliferation of basal cell progenitors, and differentation of new sensory neurons.
Transcriptional changes during neuronal death and replacement in the olfactory epithelium.
No sample metadata fields
View SamplesTransciptome analysis using a panel of WM793 melanoma cell lines following stable overexpression of wild-type or mutant forms of human NME1
Identification of a gene expression signature associated with the metastasis suppressor function of NME1: prognostic value in human melanoma.
Cell line
View SamplesHyperimmune activation is one of the strong predictors of disease progression during pathogenic immunodeficiency virus infections and is mediated in part by sustained type I interferon (IFN) signaling. Combination antiretroviral therapy suppresses hyperimmune activation only partially in HIV-infected individuals. Here, we show that blockade of Programmed Death-1 (PD-1) during chonic SIV infection significantly reduces the expression of transcripts associated with type I IFN signaling in the blood and colorectal tissue of rhesus macaques (RM). The effect of PD-1 blockade on type I IFN signaling was durable and persisted under high viremia, a condition that is seen in nonprogressive SIV infection in their natural hosts. The reduced type I IFN signaling was associated with enhanced expression of some of the junction-associated genes in the colorectal tissue and a profound decrease in LPS levels in plasma suggesting a possible repair of gut associated junctions and decreased microbial translocation. The reduced type I IFN signaling was also associated with enhanced immunity against gut resident pathogenic bacteria, control of gut associated opportunistic infections and survival of SIV-infected RMs. These results reveal novel mechanisms by which PD-1 blockade enhances survival of SIV-infected RMs and have implications for development of novel therapeutic approaches to control HIV/AIDS.
PD-1 blockade during chronic SIV infection reduces hyperimmune activation and microbial translocation in rhesus macaques.
Specimen part, Disease, Disease stage, Treatment
View SamplesAnalysis of hormone effects on irradiated LBNF1 rat testes, which contain only somatic cells except for a few type A spermatgogonia. Rats were treated for 2 weeks with either sham treatment (group X), hormonal ablation (GnRH antagonist and the androgen receptor antagonist flutamide, group XAF), testosterone supplementation (GnRH antagonist and testosterone, group XAT), and FSH supplementation ((GnRH antagonist, androgen receptor antagonist, and FSH, group XAFF). Results provide insight into identifying genes in the somatic testis cells regulated by testosterone, LH, or FSH.
Changes in gene expression in somatic cells of rat testes resulting from hormonal modulation and radiation-induced germ cell depletion.
Specimen part, Treatment
View SamplesAnalysis of LBNF1 rat testes from controls, containing both somatic and all germ cell types and from irradiated rats in which all cells germ cells except type A spermatgogonia are eliminated. Results provide insight into distinguishing germ and somatic cell genes and identification of somatic cell genes that are upregulated after irradiation.
Changes in gene expression in somatic cells of rat testes resulting from hormonal modulation and radiation-induced germ cell depletion.
Specimen part
View SamplesIn SIV/HIV infection, the gastrointestinal tissue dominates as an important site due to the impact of massive mucosal CD4 depletion and immune activation-induced tissue pathology. Unlike AIDS-susceptible rhesus macaques, natural hosts do not progress to AIDS and resolve immune activation earlier. Here, we examine the role of dendritic cells in mediating immune activation and disease progression. We demonstrate that plasmacytoid dendritic cells (pDC) in the blood upregulate 7-integrin and are rapidly recruited to the colorectum following a pathogenic SIV infection in rhesus macaques. These pDC were capable of producing proinflammatory cytokines and primed a Tc1 response in vitro. Consistent with the upregulation of 7-integrin on pDC, in vivo blockade of 47-integrin dampened pDC recruitment to the colorectum and resulted in reduced immune activation. The upregulation of 7-integrin expression on pDC in the blood was also observed in HIV-infected humans but not in chronically SIV-infected sooty mangabeys that show low levels of immune activation. Our results uncover a new mechanism by which pDC influence immune activation in colorectal tissue following pathogenic immunodeficiency virus infections.
Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques.
Specimen part
View SamplesThe biological functions of histone demethylases Jmjd3 and Utx remain poorly understood. We assessed such functions in developing T cells, using conditional (CD4-Cre-mediated) gene disruption, by inactivating Kdm6a and Kdm6b, respectively encoding Utx and Jmjd3, in immature CD4+CD8+ thymocytes. We compared microarray gene expression in mature (Va2hi CD24lo) mutant and wild-type CD4+CD8- thymocytes carrying the OT-II TCR transgene.
Histone H3 Lysine 27 demethylases Jmjd3 and Utx are required for T-cell differentiation.
Specimen part
View SamplesDespite numerous observations of effects of estrogens on spermatogenesis, identification of estrogen-regulated genes in the testis is limited. We previously showed in rats, in which irradiation had completely blocked spermatogonial differentiation, that testosterone (T) suppression with GnRH-antagonist and antiandrogen stimulated spermatogenic recovery and addition of estradiol (E2) to this regimen accelerated this recovery. We report here the global changes in testicular cell gene expression induced by the E2 treatment. By minimizing the changes in other hormones and also having concurrent data on the regulation of the genes by those hormones, we were able to dissect the effects of estrogen on gene expression, independent of gonadotropin or T changes. Expression of 20 genes, largely in somatic cells, was up- or down-regulated between 2- and 5-fold by E2. There were also early germ cell genes whose expression increased but this was a result of a small increase in spermatogonial numbers. The striking enrichment of transcripts not corresponding to known genes among the E2-downregulated probes led to the identification of one as micro-RNA miR-34a. We propose that genes whose expression levels are altered in one direction by irradiation and in the opposite direction by both T suppression and E2 treatment are candidates for controlling the block in differentiation. Several genes, including insulin-like 3 (Insl3), satisfied those criteria. If they are indeed involved in the inhibition of spermatogonial differentiation, they may be candidate targets for clinical treatments to enhance recovery of spermatogenesis following gonadotoxic exposures, such as those resulting from cancer therapy.
Estrogen-regulated genes in rat testes and their relationship to recovery of spermatogenesis after irradiation.
Specimen part, Treatment
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