We investigate the role of Snf2l in ovaries by characterizing a mouse bearing an inactivating deletion on the ATPase domain of Snf2l (Ex6DEL). Snf2l mutant mice produce significantly fewer eggs than control mice when superovulated. Thus, gonadotropin stimulation leads to a significant deficit in secondary follicles and an increase in abnormal antral follicles. We profiled the expression of granulosa cells from Snf2l WT and Ex6DEL mice treated with pregnant mares' serum gonadotropin followed by human chorionic gonadotropin
The imitation switch ATPase Snf2l is required for superovulation and regulates Fgl2 in differentiating mouse granulosa cells.
Specimen part
View SamplesExogenous 17-estradiol (E2) accelerates the progression of ovarian cancer in the transgenic tgCAG-LS-TAg mouse model of the disease. We hypothesized that E2 has direct effects on ovarian cancer cells and this study was designed to determine the molecular mechanisms by which E2 accelerates ovarian tumour progression. Mouse ovarian cancer ascites (MASE2) cell lines were derived from tgCAG-LS-TAg mice. Following intraperitoneal engraftment of MASE2 into SCID mice, exogenous E2 significantly decreased the survival time and increased the tumour burden.
17β-estradiol upregulates GREB1 and accelerates ovarian tumor progression in vivo.
No sample metadata fields
View SamplesThis experiment was set up in order to identify the (direct) transcriptional targets of the Ethylene Response Factor 115 (ERF115) transcription factor. Because ERF115 expression occurs in quiescent center (QC) cells and strong effects on the QC cells were observed in ERF115 overexpression plants, root tips were harvested for transcript profiling in order to focus on root meristem and QC specific transcriptional targets.
ERF115 controls root quiescent center cell division and stem cell replenishment.
Age, Specimen part
View SamplesWe use single-cell RNA sequencing (scRNA-seq) to explore the transcriptional changes associated with estrogen-induced dysplasia in mouse ovarian surface epithelial cells Overall design: scRNA-seq of control and estrogen-treated (100nM) mOSE cultured for 15 days. scRNA-seq was performed using the Fluidigm HT 3' RNA-seq protocol on the Fluidigm C1
Single-cell RNA-sequencing reveals transcriptional dynamics of estrogen-induced dysplasia in the ovarian surface epithelium.
Specimen part, Treatment, Subject
View SamplesGlucocorticoid resistance (GCR) is defined as an unresponsiveness to the anti-inflammatory properties of glucocorticoids (GCs) and their receptor, the glucocorticoid receptor (GR). It is a serious problem in the management of inflammatory diseases and occurs frequently. The strong pro-inflammatory cytokine TNF induces an acute form of GCR, not only in mice, but also in several cell lines, e.g. in the hepatoma cell line BWTG3, as evidenced by impaired Dexamethasone (Dex)-induced GR-dependent gene expression. We report that TNF has a significant and broad impact on the transcriptional performance of GR, but no impact on nuclear translocation, dimerization or DNA binding capacity of GR. Proteome-wide proximity-mapping (BioID), however, revealed that the GR interactome is strongly modulated by TNF. One GR cofactor that interacts significantly less with the receptor under GCR conditions is p300. NF?B activation and p300 knockdown both reduce transcriptional output of GR, whereas p300 overexpression and NF?B inhibition revert TNF-induced GCR, which is in support of a cofactor reshuffle model. This hypothesis is supported by FRET studies. This mechanism of GCR opens new avenues for therapeutic interventions in GCR diseases Overall design: Examination of GR induced gene expression in 4 conditions (1 control: NI and 3 treated: DEX, TNF, TNFDEX) starting from 3 biological replicates
TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile.
Specimen part, Cell line, Treatment, Subject
View SamplesOur lab established the M0505 cell line from the ovarian surface epithelium (OSE) of FVB/N mice in May 2005 in order to study OSE biology. This cell line spontaneously transformed into the spontaneously transformed OSE (STOSE) cell line in mid 2012.
A new spontaneously transformed syngeneic model of high-grade serous ovarian cancer with a tumor-initiating cell population.
Specimen part
View SamplesDevelopment of the female tract results from the carefull coordination of numerous signaling pathways. Here, we evaluated the role of hippo pathway in the development of the female reproductive tract.
<i>Lats1</i> and <i>Lats2</i> are required for the maintenance of multipotency in the Müllerian duct mesenchyme.
Specimen part
View SamplesTo understand how haploinsufficiency of progranulin (PGRN) protein causes frontotemporal dementia (FTD), we created induced pluripotent stem cells (iPSC) from patients carrying the GRNIVS1+5G>C mutation (FTD-iPSCs). FTD-iPSCs were fated to cortical neurons, the cells most affected in FTD and known to express PGRN. Although generation of neuroprogenitors was unaffected, their further differentiation into neurons, especially CTIP2-, FOXP2- or TBR1-TUJ1 double positive cortical neurons, was significantly decreased in FTD-neural progeny. Zinc finger nuclease-mediated introduction of PGRN cDNA into the AAVS1 locus corrected defects in cortical neurogenesis, demonstrating that PGRN haploinsufficiency causes inefficient cortical neuron generation. RNAseq analysis confirmed reversal of altered gene expression profile following genetic correction. Wnt signaling pathway, one of the top defective pathways in FTD-iPSC-derived neurons coupled with its reversal following genetic correction, makes it an important candidate. Therefore, we demonstrate for the first time that PGRN haploinsufficiency hampers corticogenesis in vitro. Overall design: We profiled 6 samples: two biological replicates for 3 conditions. Condition 1 consists of neuronal progeny derived from human Embryonic Stem Cells. Condition 2 consists of neuronal progeny derived from induced pluripotent stem cells generated from patients carrying PGRN mutation. Condition 3 consists of neuronal progeny derived from induced pluripotent stem cells generated from patients carrying PGRN mutation, genetically modified to correct the PGRN defect.
Restoration of progranulin expression rescues cortical neuron generation in an induced pluripotent stem cell model of frontotemporal dementia.
No sample metadata fields
View SamplesWe sequenced mRNA from 6 samples of FACsorted telencephalons from E14.5 Sip1|Nkx2-1 knockout and WT|Nkx2-1 control mouse embryos to find differentially expressed genes in the absence of the transcription factor Sip1. Overall design: Examination of mRNA levels in 3 control and 3 Sip1|Nkx2-1 knockout samples
Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1.
Specimen part, Cell line, Subject
View SamplesThe goal of this study was to gain insight into the molecular heterogeneity of capillary endothelial cells derived from different organs by microarray profiling of freshly isolated cells and identify transcription factors that may determine the specific gene expression profile of endothelial cells from different tissues. The study focused on heart endothelial cells and presents a validated signature of 31 genes that are highly enriched in heart endothelial cells. Within this signature 5 transcription factors were identified and the optimal combination of these transcription factors was determined for specification of the heart endothelial fingerprint.
Meox2/Tcf15 heterodimers program the heart capillary endothelium for cardiac fatty acid uptake.
Sex, Specimen part
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