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GSE143829
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Background. Primary cilia (PC) are solitary antennae present at the cell surface. These non-motile cilia play an important role in organ development and tissue homeostasis through the transduction of the Hedgehog (Hh) signaling pathway. We recently revealed the presence of PC in the epithelium of the developing epididymis, an organ of the male reproductive system whose dysfunction triggers male infertility. Acknowledging that systemic blockade of the Hh pathway trigger epididymal dysfunctions in vivo, our main goals were 1) to portray the epididymal Hh environment, 2) to determine the direct responsiveness of epididymal epithelial cells to Hh, and 3) to define the contribution of PC to the transduction of this pathway. Results. The Hh ligands Indian and Sonic hedgehog (Ihh and Shh) were respectively located in principal and clear cells of the mouse epididymis by immunofluorescent staining. The propensity of epididymal principal cells to respond to Hh signaling was assessed on immortalized epididymal DC2 cells by western-blot, confocal imaging and 3D-reconstruction. Our results indicate that epididymal principal cells secrete Ihh and expose PC that co-localize with the conventional acetylated tubulin/Arl13b ciliary markers, as well as with GLI3 Hh signaling factor. Gene expression microarray profiling indicated that the expression of 43 and 248 genes was respectively and significantly modified following pharmacological treatment of DC2 cells with the Hh agonist SAG (250 nM) or the Hh antagonist cyclopamine (20 µM) compared with the control. Among Hh target genes identified, 6.7 % presented perfect matches for GLI-transcription factor consensus sequences, and the majority belonged to interferon-dependent immune response and lipocalin 2 pathways. Finally, the contribution of epididymal PC to the transduction of canonical Hh pathway was validated by ciliobrevinD treatment, which induced a significant decrease of PC length and the expressional reduction of Hh signalling targets. Conclusions. All together our data indicate that PC from epithelial principal cells regulate gene expression profile through a possible autocrine Hh signaling. This provides new hypotheses regarding the potential contribution of PC and Hh signaling in intercellular cross-talk and immunological regulation of the epididymis.
Publication Title
Hedgehog signaling pathway regulates gene expression profile of epididymal principal cells through the primary cilium.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transcriptomic studies revealed that hundreds of mRNAs show differential expression in the brains of sleeping versus awake rats, mice, flies, and sparrows. Although these results have offered clues regarding the molecular consequences of sleep and sleep loss, their functional significance thus far has been limited. This is because the previous studies pooled transcripts from all brain cells, including neurons and glia.
Publication Title
Transcriptome profiling of sleeping, waking, and sleep deprived adult heterozygous Aldh1L1 - eGFP-L10a mice.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 280 Downloadable Samples
Illumina HiSeq 2000
Description
Parental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5’ fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during post-testicular maturation in the epididymis. We find that epididymosomes – extracellular vesicles which fuse with sperm during epididymal transit – exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. Overall design: IVF was carried out using oocytes from females fed Control diet (C) and sperm from males fed Control diet or Low Protein diet (LP). Zygotes were then developed 2 cell (2C), 4 cell (4C), 8 cell (8C), Morula (M) or Blastocyst (B) embryonic developmental stages when single embryo RNA seq was carried out to study gene expression changes.
Publication Title
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 187 Downloadable Samples
- NextSeq 500
Description
Parental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5’ fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during post-testicular maturation in the epididymis. We find that epididymosomes – extracellular vesicles which fuse with sperm during epididymal transit – exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. Overall design: Zygotes were generated by IVF from animals fed a control diet. These embryos were then microinjected with various combinations of small RNAs and control RNA (HIS3.3::GFP). Follwoing injections the zygotes were developed and allowed to develop until 2 cell (2C) or 4 cell (4C) stage when single embryo RNA seq was carried out to study gene expression changes
Publication Title
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 103 Downloadable Samples
- NextSeq 500
Description
Parental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5’ fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during post-testicular maturation in the epididymis. We find that epididymosomes – extracellular vesicles which fuse with sperm during epididymal transit – exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. Overall design: Zygotes were generated by ICSI from oocytes/females fed a Control diet and sperm/males fed either a Control or Low Protein diet. The sperm was isolated from either the Rete testis or the Cauda epididymis and injected either as a whole sperm or just the sperm head. Following fertilization by ICSI the zygotes developed for 28 hours (2C stage) and were harvested for single-embryo RNA-Seq.
Publication Title
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transcriptomic studies revealed that hundreds of mRNAs show differential expression in the brains of sleeping versus awake rats, mice, flies, and sparrows. Although these results have offered clues regarding the molecular consequences of sleep and sleep loss, their functional significance thus far has been limited. This is because the previous studies pooled transcripts from all brain cells, including neurons and glia.
Publication Title
Effects of sleep and wake on oligodendrocytes and their precursors.
Sample Metadata Fields
Specimen part
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
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of post-transcriptional regulatory networks during myeloblast-to-monocyte differentiation transition.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Treatment of leukemia cells with 1,25-dihydroxyvitamin D3 may overcome their differentiation block and lead to the transition from myeloblasts to monocytes. To identify microRNA-mRNA networks relevant for myeloid differentiation, we profiled the expression of mRNAs and microRNAs associated to the low- and high-density ribosomal fractions in leukemic cells and in their differentiated monocytic counterpart. Intersection between mRNAs shifted across the fractions after treatment with putative target genes of modulated microRNAs showed a series of molecular networks relevant for the monocyte cell fate determination
Publication Title
Identification of post-transcriptional regulatory networks during myeloblast-to-monocyte differentiation transition.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
In rodents, the uterus of a mature
Publication Title
Fine temporal analysis of DHT transcriptional modulation of the ATM/Gadd45g signaling pathways in the mouse uterus.
Sample Metadata Fields
No sample metadata fields
View Samples