Despite 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
View SamplesHuman adipose stem cells (ASCs) have been shown, in pre-clinical studies, to have therapeutic applicability in diverse fields, but a standard expansion method for clinical applications remains yet to be established. Isolated ASCs are typically expanded in medium containing fetal bovine serum (FBS). However, sera and other animal-derived culture reagents stage numerous safety issues in clinical therapy, including possible infections and severe immune reactions. By expanding the ASCs in medium containing human serum (HS), the problem can be eliminated.
Differential gene expression in adipose stem cells cultured in allogeneic human serum versus fetal bovine serum.
Specimen part
View SamplesCell lines geneticially engineered to undergo conditional asymmetric self-renewal were used to identify genes whose expression is asymmetric self-renewal associated (ASRA). Non-random sister chromatid segregation occurs concordantly with asymmetric self-renewal in these cell lines.
A resource for discovering specific and universal biomarkers for distributed stem cells.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DEMETER plant DNA demethylase induces antiviral response by interferon signalling in animal cells.
Specimen part, Time
View SamplesExpression profiles of human embryonic kidney (HEK)-293T cells expressing a GFP (293T-GFP) or a truncated form of Arabidopsis DEMETER (DME) 5-methylcytosine (5mC) DNA glycosylase (293T-DME) analyzed on an Affymetrix Human Genome U133 Plus 2.0 Array Platform. These array data revealed differentially expressed genes (DEGs) between the 293T-GFP cells (without direct 5mC excision activity) and 293T-DME cells (with artificially implemented direct 5mC excision activity).
DEMETER plant DNA demethylase induces antiviral response by interferon signalling in animal cells.
Specimen part, Time
View SamplesTranscriptional profiling of mouse fibroblast-like synoviocytes (FLS) comparing FLS infected with empty adenovirus and Epas1 adenovirus. RNA was extracted from each FLS. We used microarrays to determine the effect of Epas1 overexpression on FLS and identifying the noble regulatory molecules during rheumatoid arthritic pathogenesis
Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis.
Specimen part
View SamplesThe jmjC-domain containing H3K4 histone demethylase JARID1B/KDM5B/PLU1 is over-expressed in human breast cancer and is a potential target for breast cancer treatment. To investigate the in vivo function of JARID1B, we developed a new strain of Jarid1b knockout mice and characterized the phenotypes in detail. Unlike previously reported knockout strains, the majority of our Jarid1b knockout mice are viable beyond embryonic and neonatal stages. Nonetheless, these mice exhibit decreased body weight, higher incidence of adult mortality and decreased female fertility. Furthermore, Jarid1b knockout mice show delayed mammary gland development. Mechanistically, loss of JARID1B leads to decreased serum estrogen levels and reduced proliferation of mammary epithelial cells in early puberty. In addition, in mammary epithelial cells, loss of JARID1B diminishes the expression of key regulators of mammary morphogenesis, including FOXA1, estrogen receptor (ER), and GATA3. Taken together, these results indicate that JARID1B positively regulates mammary ductal development through both extrinsic and cell-autonomous mechanisms.
Histone demethylase jumonji AT-rich interactive domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes.
Specimen part
View SamplesPurpose: The goals of this experiments are to analyze the transcriptomic change in dyrk1aakrb1 mutants compared with WT embryos by mRNA-seq technique. Methods: Whole mRNA profiles of 32 hpf WT(+/+) and dyrk1aakrb1 mutants zebrafish embryos were generated by mRNA-seq techinque, in duplicate, using HiSeq 2500 (Illumina, Inc., USA). Results: This analysis identified 354 transcripts as differentially regulated genes (DEG), of which 125 were up-regulated and 229 were down-regulated in dyrk1aakrb1 mutant (more than 2 fold and less than 0.5 fold respectively,; p value< 0.05). Overall design: Whole transcriptomic analysis of zebrafish embryos of dyrk1aakrb1, dyrk1aa knock out mutant and WT (+/+) in the background of Tg(kdrl:egfp) at 32 hpf.
Vascular defects of <i>DYRK1A</i> knockouts are ameliorated by modulating calcium signaling in zebrafish.
Age, Specimen part, Subject
View SamplesPurpose: The goals of this experiments are to analyze the transcriptomic change in dyrk1aakrb1 mutants compared with WT embryos by mRNA-seq technique. Methods: Whole mRNA profiles of 48 hpf WT(+/+) and dyrk1aakrb1 mutants zebrafish embryos were generated by mRNA-seq techinque, in duplicate, using HiSeq 2500 (Illumina, Inc., USA). Results: This analysis identified 222 transcripts as differentially regulated genes (DEG), of which 101 were up-regulated and 121 were down-regulated in dyrk1aakrb1 mutant (more than 2 fold and less than 0.5 fold respectively,; p value< 0.05). Overall design: Whole transcriptomic analysis of zebrafish embryos of dyrk1aakrb1, dyrk1aa knock out mutant and WT (+/+) in the background of Tg(kdrl:egfp) at 48 hpf.
Vascular defects of <i>DYRK1A</i> knockouts are ameliorated by modulating calcium signaling in zebrafish.
Specimen part, Subject
View SamplesTissue inflammation is a key factor underlying insulin resistance in established obesity. Several models of immuno-compromised mice are protected from obesity-induced insulin resistance. However, it is unanswered whether inflammation triggers systemic insulin resistance or vice versa in obesity. The purpose of this study was to assess these questions.
Lipid-overloaded enlarged adipocytes provoke insulin resistance independent of inflammation.
Specimen part, Treatment, Time
View Samples