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SRP044747
Mus musculus
16 Downloadable Samples
Illumina Genome Analyzer II
Description
Sertoli cells (SCs), the only somatic cells within seminiferous tubules, associate intimately with developing germ cells. They not only provide physical and nutritional support but also secrete factors essential to the complex developmental processes of germ cell proliferation and differentiation. The SC transcriptome must therefore adapt rapidly during the different stages of spermatogenesis. We report comprehensive genome-wide expression profiles of pure populations of SCs isolated at 5 distinct stages of the first wave of mouse spermatogenesis, using RNA sequencing technology. We were able to reconstruct about 13 901 high-confidence, nonredundant coding and noncoding transcripts, characterized by complex alternative splicing patterns with more than 45% comprising novel isoforms of known genes. Interestingly, roughly one-fifth (2939) of these genes exhibited a dynamic expression profile reflecting the evolving role of SCs during the progression of spermatogenesis, with stage-specific expression of genes involved in biological processes such as cell cycle regulation, metabolism and energy production, retinoic acid synthesis, and blood-testis barrier biogenesis. Finally, regulatory network analysis identified the transcription factors endothelial PAS domain-containing protein 1 (EPAS1/Hif2a), aryl hydrocarbon receptor nuclear translocator (ARNT/Hif1ß), and signal transducer and activator of transcription 1 (STAT1) as potential master regulators driving the SC transcriptional program. Our results highlight the plastic transcriptional landscape of SCs during the progression of spermatogenesis and provide valuable resources to better understand SC function and spermatogenesis and its related disorders, such as male infertility. Overall design: Genome-wide expression profiling analysis using Illumina next-generation sequencing technology
Publication Title
Research resource: the dynamic transcriptional profile of sertoli cells during the progression of spermatogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The human seminal plasma is a potential source of biomarkers for male reproductive disorders. A tissue-profiling analysis of the main organs participating in the secretion of this body fluid was conducted to identify tissue-specific genes along the male reproductive tract.
Publication Title
Identification of genital tract markers in the human seminal plasma using an integrative genomics approach.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 15 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
We used microarray analysis to further our understanding of the mode of action of the well know caloric restriction mimetic rapamycin and the compound Allantoin first studied in the context of aging in this study. His work helps build on our understanding of potential caloric restriction mimetics predicted from our bioinformatic aproach of quering the Connectivity Map, a database of drug-induced gene expression profiles, using the transcriptional profile of CR to identify drugs that induce a similar or opposite gene expression profile.
Publication Title
A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens, Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
CREB3L1 is a metastasis suppressor that represses expression of genes regulating metastasis, invasion, and angiogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The unfolded protein response (UPR) is activated in response to hypoxia-induced stress such as in the tumor microenvironment. This study examined the role of CREB3L1 (cAMP-responsive element-binding protein 3-like protein 1), a member of the UPR, in breast cancer development and metastasis. Initial experiments identified the loss of CREB3L1 expression in metastatic breast cancer cell lines compared to low- or non-metastatic cell lines. When metastatic cells were transfected with CREB3L1 they demonstrated reduced invasion and migration in vitro, as well as a significantly decreased ability to survive under non-adherent or hypoxic conditions. Interestingly, in an in vivo rat mammary tumor model, CREB3L1 expressing cells not only failed to form metastases compared to CREB3L1 null cells but regression of the primary tumors was seen in 70% of the animals as a result of impaired angiogenesis. Microarray and ChIP on Chip analyses identified changes in the expression of many genes involved in cancer development and metastasis, including a decrease in those involved in angiogenesis. These data suggest that CREB3L1 plays an important role in suppressing tumorgenesis and loss of expression is required for the development of a metastatic phenotype.
Publication Title
CREB3L1 is a metastasis suppressor that represses expression of genes regulating metastasis, invasion, and angiogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Platelets have multiple roles in cancer cell metastasis. In this work we employed exon microarray technology to address platelet gene expression in metastatic non small cell lung cancer versus controls without cancer. We found that 197 of the 200 genes with the most significantly altered expression levels had their expression levels downregulated.
Publication Title
Significant downregulation of platelet gene expression in metastatic lung cancer.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
17-HSD1 expression modulates T47D transcript profile in in steroid-deprived medium. The enzyme specifically regulates apoptosis and cancer-related genes in T47D cells cultured in steroid-deprived medium. Genes that primarily involved in Cell cycle progression, such as the Cyclin A2 gene, CCNA2, are generally down-regulated whereas most genes involved in apoptosis and cell death, such as the proapoptotic gene XAF1 and FGF12, are on the contrary up-regulated by 17-HSD1 knockdown, and 21% of the modulated genes belong to this latter functional category. This correborates with its role previously shown in increasing breast cancer cell proliferation (Aka et al, 2010) and indicates that in addition to its direct role as cell proliferation via incresing E2 and decreasing DHT, 17-HSD1 may also be involved in oncogenesis by favoring its anti-apoptosis pathway in breast cancer cells 17-HSD1 may also be involved in oncogenesis by favoring anti-apoptosis pathway and/or inhibiting cell survival pathway. We tested the ability of estrogen to induce or repress endogenous genes of T47D by microarray analysis. A total of 131 genes were found to increase or decrease 1.5-fold or higher in response to 17 beta-estradiol (1 nM for 48 h). Besides, the gene regulation occuring in steroid-deprived conditions showed that 17-HSD1 modulates gene expression in steroid-independent manners. Our study thus demonstrates that 17-HSD1 modulates the E2-independent transcription of endogenous genes in T47D cells. The E2-dependent transcription as well as the E2-independent transcription are significantly modulated by 17-HSD1 in breast cancer cells We first report here that breast cancer cell transcript profile is independtly modulated by both 17-HSD1 and its principale product estradiol.
Publication Title
Estradiol-independent modulation of breast cancer transcript profile by 17beta-hydroxysteroid dehydrogenase type 1.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of the gene expression pattern in the caput, corpus and cauda epididymides of three donors of 26-50 years of age with no medical pathologies that could affect reproductive function. The data generated in this study demonstrate a region specific gene expression pattern along the human epididymis that seems to coincide with the morphological distinctive features of the excurrent duct.
Publication Title
Region-specific gene expression profiling along the human epididymis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The efficacy and exceptionally good tolerance of estrogen blockade in the treatment of breast cancer is well recognized but novel agents are required, especially to take advantage of the multiple consecutive responses obtained in breast cancer progressing following previous hormone therapy, thus delaying the use of cytotoxic chemotherapy with its usually serious side effects. Acolbifene (ACOL) is a novel and unique antiestrogen completely free of estrogen-like activity in both the mammary gland and uterus while preventing bone loss. From the preclinical and clinical data so-far available, this new antiestrogen represents a unique opportunity for a highly potent and specific blockade of estrogen action in the mammary gland and uterus while exerting estrogen-like beneficial effects in other tissues (selective estrogen receptor modulator or SERM activity). In order to better understand the specificity of action of acolbifene, we have used Affymetrix GeneChips containing 45,000 probe sets to analyze 34,000 genes to determine the specificity of this compound compared to the pure antiestrogen fulvestrant, as well as the mixed antagonists/agonists tamoxifen and raloxifene to block the effect of estradiol (E2) and to induce effects of their own on gene expression in the mouse mammary gland. The genes modulated by E2 were those identified in two separate experiments and validated by quantitative real-time PCR (Q_RT-PCR). Three hours after the single subcutaneous injection of E2 (0.05 ug), the simultaneous administration of acolbifene, fulvestrant, tamoxifen and raloxifene blocked by 98%, 62%, 43% and 92% the number of E2-upregulated genes, respectively. On the other hand, 70%, 10%, 25% and 55% of the genes down-regulated by E2 were blocked by the same compounds. Acolbifene was also the compound which, when used alone, modulated the smallest number of genes also influenced by E2, namely 4%, thus possibly explaining the potent tumoricidal action of this compound in human breast cancer xenografts where 61% of tumors disappeared, thus bringing a new paradigm in the hormonal therapy of breast cancer.
Publication Title
Specific transcriptional response of four blockers of estrogen receptors on estradiol-modulated genes in the mouse mammary gland.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Worldwide, almost 100 millions men rely on vasectomy for male contraceptive purposes. Due to changes in their personal life, an increasing number of these men request surgical vasectomy reversal. Unfortunately, a significant proportion of these men remain infertile, despite the reestablishment of patent ducts, possibly due to epididymal damages caused by vasectomy. In animal models, vasectomy affects different epididymal physiological and biochemical parameters. However, consequences of vasectomy on these biochemical parameters are poorly understood at the molecular level. Furthermore, results obtained with animal models cannot by extrapolated to human to understand the consequences of vasectomy on epididymal functions. Gene expression pattern of epididimydis is highly regulated. We previously showed that the human epididymal expression pattern of two genes is altered under vasectomy. To complete the list of epididymal genes affected by vasectomy, we analysed the epididymal gene expression profile of three vasectomised donors, using the affymetrix human GeneChip U133 Plus 2. These results were compared with gene expression pattern of three normal donors. The data generated allowed the identification of many human epididymal genes for which the expression is modified under vasectomy. Qt-PCR and western-blot analysis of six selected genes known to be expressed in specific epididymal segments were performed. The Qt-PCR results confirmed the selected transcripts expression pattern deduced from microarrays data, while the western-blot analysis revealed some differences in protein distribution along the epididymis when compared to the transcripts expression pattern. These results contribute to the understanding of the causes of the persistent of infertility even though spermogram values suggest surgical success of vasovasostomy.
Publication Title
Effects of vasectomy on gene expression profiling along the human epididymis.
Sample Metadata Fields
No sample metadata fields
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