NSAIDs and ACE that affect prostaglandin synthesis are widely used by pregnant women. Epidemiological studies have hypothesized a potential relation of testis dysgenesis syndromes such as cryptorchidism and hypospadias to exposure to these molecules during both the first and the second trimesters of gestation. To decipher whether the embryonic gonads themselves are targets for these molecules, we analysed the impact of precocious in utero exposure to NSAIDs and ACE alone or in combination on the early development of the testis during sex determination, using therapeutic doses similar to those administrated in human medications. We found that in utero exposure to ACE, aspirin or ibuprofen affects the germ cell proliferation in embryonic testis. The whole transcriptome of 13.5 dpc (days post coïtum) treated testis suggests different mechanisms of action of these drugs and a functional interaction between both molecules used in combination, in accelerating the germ cell differentiation. We identified that ACE and ibuprofen exposure through the up-regulation of Dnmt3L expression induces advanced epigenetic reprograming of the germline and enhanced glycogen storage within the testis cords through the activation of extracellular matrix genes expression. In addition, we identified for the first time the prostaglandin production pattern in the embryonic gonad and showed that PGD2, PGE2 and PGI2 were the targets of ACE and NSAIDs drugs. These features might affect the formation and maturation of postnatal testis and secondary reproductive organs leading to male infertility in adult age. Overall design: examination of the impact of in utero exposure to NSAIDs and ACE on testis organogenesis
Intergenerational effects on mouse sperm quality after in utero exposure to acetaminophen and ibuprofen.
Specimen part, Cell line, Treatment, Subject
View SamplesTumor protein p53 is a key regulator of several cellular pathways, including DNA repair, cell cycle and angiogenesis. Kevetrin exhibits p53-dependent as well as independent activity in solid tumors, while its effects on leukemic cells remain unknown. We analyzed the response of acute myeloid leukemia (AML) cell lines (TP53 wild-type: OCI-AML3 and MOLM-13; and TP53-mutant: KASUMI-1 and NOMO-1) to kevetrin at a concentration range of 85-340 μM. Kevetrin induced cell growth arrest and apoptosis in all cell lines and in primary cells, with TP53-mutant models displaying a higher sensitivity and p53 induction. Gene expression profiling revealed a common core transcriptional program altered by drug exposure and the downregulation of glycolysis, DNA repair and unfolded protein response signatures. These findings suggest that kevetrin may be a promising therapeutic option for patients with both wild-type and TP53-mutant AML.
Kevetrin induces apoptosis in TP53 wild‑type and mutant acute myeloid leukemia cells.
Treatment
View SamplesWe sequenced mRNA extracted from heads of a D. melanogaster population that was sedated with a stream of ethanol saturated vapor, 30 minutes before RNA extraction; and from an age-matched untreated control group. Differential gene expression between the two groups was calculated and reported. Overall design: Examination of mRNA levels in heads of D. melanogaster adult females after ethanol exposure was performed using next generation sequencing (NGS) technology.
Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway.
Cell line, Treatment, Subject
View SamplesChoroid plexuses (CP) develop early during development. They form a barrier between the blood and the cerebrospinal fluid, and fulfill important protective and nutritive functions. We used Affymetrix microarrays to assess whether CP of the lateral ventricles (LVCP) have similar functions in developing and adult brain. We identified distinct families of protective and transport genes and found that most of these genes were already well expressed during development.
Developmental changes in the transcriptome of the rat choroid plexus in relation to neuroprotection.
Specimen part
View SamplesRNA from circulating blood reticulocytes was utilized to provide a robust description of genes transcribed at the final stages of erythroblast maturation. After depletion of leukocytes and platelets, Affymetrix HG-U133 arrays were hybridized with probe from total RNA isolated from blood sampled from 14 umbilical cords and 14 healthy adult humans.
The human reticulocyte transcriptome.
No sample metadata fields
View SamplesHuman ES or iPS Cells were differentiated into endothelial cells (ECs) defined by expression of CD31 (PECAM1) and CD144 (VE-Cadherin) on the cell surface. All ES or iPS derived ECs were greater than 90% double positive for these two markers.
Limited gene expression variation in human embryonic stem cell and induced pluripotent stem cell-derived endothelial cells.
Specimen part
View SamplesSatellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved during early postnatal growth till acquisition of satellite cell quiescence.
Pericytes in the myovascular niche promote post-natal myofiber growth and satellite cell quiescence.
Specimen part
View Samplesdifferential expression between wild-type pistils of Arabidopsis thaliana at late 11 to late 12 floral stages, and similar stage pistils of coatlique mutant which lacks a functional embryo sac
Genetic subtraction profiling identifies genes essential for Arabidopsis reproduction and reveals interaction between the female gametophyte and the maternal sporophyte.
Specimen part
View SamplesmESCs cultured in microfluidic chambers secrete endogneous signals which accumulate to facilitate expression of pluripotency associated genes
Embryonic Stem Cells Cultured in Microfluidic Chambers Take Control of Their Fate by Producing Endogenous Signals Including LIF.
Cell line
View SamplesTo study the effect of structural changes on expression, we assessed gene expression in genomic disorder mouse models. Both a microdeletion and its reciprocal microduplication mapping to mouse chromosome 11 (MMU11), which model the rearrangements present in Smith-Magenis (SMS) and Potocki-Lupski (PTLS) syndromes patients, respectively, have been engineered. We profiled the transcriptome of five different tissues affected in human patients in mice with 1n (Deletion/+), 2n (+/+), 3n (Duplication/+) and uniallelic 2n (Deletion/Duplication) copies of the same region in an identical genetic background. The most differentially expressed transcripts between the four studied genotypes were ranked. A highly significant propensity, are mapping to the engineered SMS/PTLS interval in the different tissues. A statistically significant overrepresentation of the genes mapping to the flanks of the engineered interval was also found in the top-ranked differentially expressed genes. A phenomenon efficient across multiple cell lineages and that extends along the entire length of the chromosome, tens of megabases from the breakpoints. These long-range effects are unidirectional and uncoupled from the number of copies of the copy number variation (CNV) genes. Thus, our results suggest that the assortment of genes mapping to a chromosome is not random. They also indicate that a structural change at a given position of the human genome may cause the same perturbation in particular pathways regardless of gene dosage. An issue that should be considered in appreciating the contribution of this class of variation to phenotypic features.
Phenotypic consequences of copy number variation: insights from Smith-Magenis and Potocki-Lupski syndrome mouse models.
Sex
View Samples