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Mus musculus
8 Downloadable Samples
Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Resistance towards anti-angiogenic therapy (AAT) still represents a substantial clinical challenge. We report here that tumor-infiltrating mast cells (MC) are powerful mediators decreasing efficacy of AAT in mice and cancer patients. They act in a cell-extrinsic manner by secreting granzyme B, which liberates pro-angiogenic mediators from the extracellular matrix. In addition, MC also diminish efficacy of anti-angiogenic agents in a cell-autonomous way, which can be blocked by the mast cell degranulation inhibitor cromolyn. Our findings are relevant in humans because patients harboring higher numbers of MC in their tumors have an inferior outcome after anti-angiogenic treatment in the Gepar Quinto randomized Phase 3 clinical trial. Thus, MC-targeting might represent a novel promising approach to increase efficacy of AAT.
Publication Title
Mast cells decrease efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme B.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The platelet-derived growth factor receptor alpha (PDGFR) exhibits divergent effects in skeletal muscle. At physiological levels, signaling through this receptor promotes muscle development in growing embryos and proper angiogenesis in regenerating adult muscle. However, either increased PDGF ligands or enhanced PDGFR pathway activity causes pathological fibrosis. This excessive collagen deposition, which is seen in aged and diseased muscle, interferes with proper muscle function and limits the effectiveness of gene- and cell-based therapies for muscle disorders. Although compelling evidence exists for the role of PDGFR in fibrosis, little is known about the cells through which this pathway acts. Here we show that PDGFR signaling regulates a population of muscle-resident fibro/adipogenic progenitors (FAPs) that play a supportive role in muscle regeneration but may also cause fibrosis when aberrantly regulated. We found that FAPs produce multiple transcriptional variants of PDGFR with different polyadenylation sites, including an intronic variant that codes for a protein isoform containing a truncated kinase domain. This variant, upregulated during regeneration, acts as a decoy to inhibit PDGF signaling and to prevent FAP over-activation. Moreover, increasing expression of this isoform limits fibrosis in vivo, suggesting both biological relevance and therapeutic potential of modulating polyadenylation patterns in stem cell populations.
Publication Title
Intronic polyadenylation of PDGFRα in resident stem cells attenuates muscle fibrosis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina Genome Analyzer IIx
Description
The granulosa cells in the mammalian ovarian follicle respond to gonadotropin signalling and are involved in the processes of folliculogenesis and oocyte maturation. Studies on gene expression and regulation in human granulosa cells are of interest due to their potential for estimating the oocyte viability and IVF success. However, the post-transcriptional gene expression studies on miRNA level in the human ovary have been scarce. The current study determined the miRNA profile by deep sequencing of the two intrafollicular somatic cell types: mural and cumulus granulosa cells isolated from women undergoing controlled ovarian stimulation and in vitro fertilization. Overall design: Paired cumulus and mural granulosa samples were analysed from 3 women participating in IVF procedure. Libraries of all 6 samples were sequenced twice, generating 2 technical replicates for each sample. Differential gene expression study was performed on the pooled results of technical replicates.
Publication Title
Research resource: small RNA-seq of human granulosa cells reveals miRNAs in FSHR and aromatase genes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The platelet-derived growth factor receptor alpha (PDGFR) exhibits divergent effects in skeletal muscle. At physiological levels, signaling through this receptor promotes muscle development in growing embryos and proper angiogenesis in regenerating adult muscle. However, either increased PDGF ligands or enhanced PDGFR pathway activity causes pathological fibrosis. This excessive collagen deposition, which is seen in aged and diseased muscle, interferes with proper muscle function and limits the effectiveness of gene- and cell-based therapies for muscle disorders. Although compelling evidence exists for the role of PDGFR in fibrosis, little is known about the cells through which this pathway acts. Here we show that PDGFR signaling regulates a population of muscle-resident fibro/adipogenic progenitors (FAPs) that play a supportive role in muscle regeneration but may also cause fibrosis when aberrantly regulated. We found that FAPs produce multiple transcriptional variants of PDGFR with different polyadenylation sites, including an intronic variant that codes for a protein isoform containing a truncated kinase domain. This variant, upregulated during regeneration, acts as a decoy to inhibit PDGF signaling and to prevent FAP over-activation. Moreover, increasing expression of this isoform limits fibrosis in vivo, suggesting both biological relevance and therapeutic potential of modulating polyadenylation patterns in stem cell populations.
Publication Title
Intronic polyadenylation of PDGFRα in resident stem cells attenuates muscle fibrosis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
The granulosa cells in the mammalian ovarian follicle respond to gonadotropin signalling and are involved in the processes of folliculogenesis and oocyte maturation. Studies on gene expression and regulation in human granulosa cells are of interest due to their potential for estimating the oocyte viability and IVF success. The current study determined the mRNA profile by deep sequencing of the two intrafollicular somatic cell types: mural and cumulus granulosa cells isolated from women undergoing controlled ovarian stimulation and in vitro fertilization. Overall design: Paired cumulus and mural granulosa samples were analysed from 3 women participating in IVF procedure. Differential gene expression study was performed. The identified gene expression profile was also used for predicting targets for miRNAs that were also identified from the same samples (GSE46489).
Publication Title
Research resource: small RNA-seq of human granulosa cells reveals miRNAs in FSHR and aromatase genes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Communication between various ovarian cell types is a prerequisite for folliculogenesis and ovulation. In antral follicles granulosa cells divide into two distinct populations of mural (MGC) and cumulus granulosa cells (CGC), enveloping the antrum and surrounding the oocyte, respectively. IVF offers a good opportunity for analysing their functional properties since granulosa cells can be retrieved during the puncturing procedure of stimulated follicles. The aim of this study was to compare the transcriptomes of MGC and CGC in stimulated antral follicles obtained from 19 women undergoing IVF-ICSI procedure. MGC were obtained from follicular fluid and CGC were acquired after oocyte denudation for micromanipulation. Gene expression analysis was conducted using the genome-wide Affymetrix transcriptome array. The expression profile of the two granulosa cell populations varied significantly. Out of 28 869 analysed transcripts 4 480 were differentially expressed (q-value < 10-4) and 489 showed 2-fold difference in the expression level with 222 genes up-regulated in MGC and 267 in CGC. The transcriptome of MGC showed higher expression of genes involved in immune response, hematological system function and organismal injury, while CGC had genes involved in protein degradation and nervous system function up-regulated. Cell-to-cell signalling and interaction pathways were noted in both cell populations. Furthermore, numerous novel transcripts that have not been previously described in follicular physiology were identified. In conclusion, our results provide a solid basis for future studies in follicular biology that will help to identify molecular markers for oocyte and embryo viability in IVF.
Publication Title
The differential transcriptome and ontology profiles of floating and cumulus granulosa cells in stimulated human antral follicles.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
P6 ID4-EGFP+ undifferentiated spermatogonia, including those stained robustly (high) or weakly (low) for TSPAN8 were isolated by FACS. Overall design: Three replicate preparations of each population were used for independent RNA-seq using SMART-seq v4, Nextera XT libraries, Hiseq2500 sequencing, and TopHat/Bowtie/Cufflinks analyses.
Publication Title
TSPAN8 Expression Distinguishes Spermatogonial Stem Cells in the Prepubertal Mouse Testis.
Sample Metadata Fields
Cell line, Subject
View Samples
SRP040772- Homo sapiens
- 11 Downloadable Samples
- IlluminaGenomeAnalyzer
Description
miRNA high-throughput sequencing was used to investigate endometriosis lesion-specific miRNA expression profiles by comparing a set of paired samples of peritoneal endometriotic lesions and matched healthy surrounding tissue together with eutopic endometrium of the same patients. We found that miRNAs of surrounding peritoneal tissue mask most of the miRNA expression differences that could originate from endometriotic tissue and thus only miRNAs with significantly different levels in the endometriotic lesions compared to peritoneal tissue were detected. According to the results of this study, two miRNAs – miR-34c and miR-449a showed remarkably higher expression in lesions compared to healthy tissue. Overall design: Eleven tissue samples (two endometria, five peritoneal lesions and four matched adjacent normal-appearing tissues) were analysed from two patients with a histologically confirmed diagnosis of moderate-severe endometriosis (III-IV stage)
Publication Title
High-throughput sequencing approach uncovers the miRNome of peritoneal endometriotic lesions and adjacent healthy tissues.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos taurus
- 36 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Liver plays a profound role in the acute phase response (APR) observed in the early phase of acute bovine mastitis caused by Escherichia coli (E. coli). To gain an insight into the genes and pathways involved in hepatic APR of dairy cows we performed a global gene expression analysis of liver tissue sampled at different time points before and after intra-mammary (IM) exposure to E. coli lipopolysaccharide (LPS) treatment.
Publication Title
Gene expression profiling of liver from dairy cows treated intra-mammary with lipopolysaccharide.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
TRF2 is a paralogue of TATA-box binding protein (TBP) with highest expression in testis. Although Trf2 inactivation in mice leads to arrested spermatogenesis, there is no direct evidence that Trf2 is recruited to chromatin to directly regulate gene expression. We used genetically modified mice where endogenous Trf2 has been modified to carry a TAP-TAG to perform ChIP-reChIP followed by deep sequencing. We found that Trf2 is recruited to all active promoters as a subunit of TFIIA/ALF complex together with TBP. To assess the effect of Trf2 inactivation on gene expression we performed RNA-seq on WT and Trf2-/- testes at 21 days of age when haploid cell gene expression is activated. Overall design: The testes from three 21 day old WT and three Trf2-/- males were taken to prepare total RNAs for deep sequencing.
Publication Title
TRF2 is recruited to the pre-initiation complex as a testis-specific subunit of TFIIA/ALF to promote haploid cell gene expression.
Sample Metadata Fields
Specimen part, Subject
View Samples