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SRP069029
Mus musculus
144 Downloadable Samples
Illumina HiSeq 2000
Description
Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the regulation of pituitary transcription factors Hesx1 and Pit1. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome wide analysis of PROP1 DNA binding and effects on gene expression in mutant tissues, isolated stem cells and engineered cell lines. We determined that PROP1 is essential for maintaining proliferation of stem cells and stimulating them to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to and represses claudin 23, characteristic of epithelial cells, and it activates EMT inducer genes: Zeb2, Notch2 and Gli2. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation. Overall design: Pituitary Colony forming cells mRNA of 13-day old wild type (Prop1 +/+), Prop1 mutants (Prop1df/df), wild type (Pit1+/+) and Pit1 mutants (Pit1 dw/dw) mice were generated by deep sequencing, in triplicates.
Publication Title
PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Bos taurus
- 15 Downloadable Samples
Affymetrix Bovine Genome Array (bovine)
Description
Fetal spleens were collected at days 82 and 97 of gestation following maternal infection with BVDV on day 75 of gestation.
Publication Title
Attenuated lymphocyte activation leads to the development of immunotolerance in bovine fetuses persistently infected with bovine viral diarrhea virus†.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 98 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Triple-negative (TN) breast cancers need to be refined in order to identify therapeutic subgroups of patients.
Publication Title
Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Nuclear lamin B1 constitutes one of the major structural proteins in the lamina mesh. We silenced the expression of lamin B1 by RNA interference in the colon cancer cell line DLD-1 and showed a dramatic redistribution of H3K27me3 from the periphery to a more homogeneous nuclear dispersion; in addition we observed an increased frequency of micronuclei and nuclear blebs. By 3D-FISH analyses, we demonstrate that the volume and surface of chromosome territories were significantly larger in LMNB1-depleted cells, suggesting that lamin B1 is required to maintain chromatin condensation in interphase nuclei. These changes led to a prolonged S-phase due to activation of Chk1 and telomere attrition. Finally, silencing of LMNB1 resulted in extensive changes in alternative splicing of multiple genes and in a higher number of enlarged nuclear speckles. Taken together, our results suggest a mechanistic role of the nuclear lamina in the organization of chromosome territories, maintenance of genome integrity and proper gene splicing.
Publication Title
Loss of lamin B1 results in prolongation of S phase and decondensation of chromosome territories.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 4000
Description
Transcription factors and signaling pathways that regulate stem cells and specialized hormone-producing cells in the pituitary gland have been the subject of intense study and have yielded a mechanistic understanding of pituitary organogenesis and disease. Yet, the regulation of stem cell proliferation and differentiation, the heterogeneity among specialized hormone-producing cells, and the role of non-endocrine cells in the gland remain important, unanswered questions. Recent advances in single-cell RNA sequencing (scRNAseq) technologies provide new avenues to address these questions. We performed scRNAseq on approximately 13,663 cells pooled from six whole pituitary glands of 7-week-old C57BL/6 male mice. We identified pituitary endocrine and stem cells in silico, as well as other support cell-types such as endothelia, connective tissue, and red and white blood cells. Differential gene expression analyses identify known and novel markers of pituitary endocrine and stem cell populations. We demonstrate the value of scRNAseq by in vivo validation of a novel gonadotrope-enriched marker, Foxp2. We present novel scRNAseq data of in vivo pituitary tissue, including data from agnostic clustering algorithms which suggest the presence of a somatotrope subpopulation enriched in sterol/cholesterol synthesis genes. At the same time, we show that incomplete transcriptome annotation can cause false negatives on some scRNAseq platforms that only generate 3' transcript end sequences, and use in vivo data to recover reads of the pituitary transcription factor Prop1. Ultimately, scRNAseq technologies represent a significant opportunity to address longstanding questions regarding the development and function of the different populations of the pituitary gland throughout life. Overall design: 10x Chromium single-cell RNAseq of cells from pituitary glands of 7-week-old male C57BL/6 mice
Publication Title
Single-Cell RNA Sequencing Reveals Novel Markers of Male Pituitary Stem Cells and Hormone-Producing Cell Types.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
Purpose: We aimed to identify miRNAs which are induced by the Activin/Nodal effectors, P-Smad2/3, in order to further our understanding of how P-Smad2/3 controls downstream gene expression in mouse ES cells to regulate crucial biological processes. Methods: We used a previously developed Tetracycline-On (Tet-On) system (TAG1) to manipulate the levels of P-Smad2/3 in mouse ES cells and performed an Illumina deep-sequencing screen to identify miRNAs which followed the P-Smad2/3 pathway. Results: We filtered the deep-seq data to identify a list of 28 miRNAs which showed a >1.25 fold increase in response to P-Smad2/3 induction and a >1.25 fold decrease in response to P-Smad2/3 repression. Conclusions: Our study represents a comprehensive global profiling of miRNA expression in response to changes in P-Smad2/3 levels in mouse ES cells. Overall design: miRNA profiles of TAG1 cells which were untreated (control), SB-431541 treated (P-Smad2/3 repressed), or Dox treated (P-Smad2/3 induced), were generated using Illumina GAII.
Publication Title
TGF-β/Smad2/3 signaling directly regulates several miRNAs in mouse ES cells and early embryos.
Sample Metadata Fields
Specimen part, Subject
View Samples- Bos taurus
- 18 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
The response to the presence of the ncpBVDV-infected PI or TI fetus is expected to provide information on the impact of the PI fetus on the immune response of the dam
Publication Title
Persistent fetal infection with bovine viral diarrhea virus differentially affects maternal blood cell signal transduction pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina Genome Analyzer II
Description
OBJECTIVE: MicroRNAs (miRNAs, miRs), a class of small non-coding RNA molecules, are posttranscriptional regulators involved in a plethora of cellular functions and have been proposed as potential therapeutic targets in various diseases, including rheumatoid arthritis (RA). In this study, we sought to discover novel miR associations in synovial fibroblasts (SFs), a key cell type mediating RA pathogenesis, by performing miR expression profiling on cells isolated from the human TNF transgenic mouse model (TghuTNF or Tg197). METHODS: miR expression in SFs isolated from 8-week-old, fully diseased TghuTNF and WT littermate control mice were determined by deep sequencing of small RNAs and the arthritic profile was established by pairwise comparisons of the two groups. qRT-PCR analysis was utilised for profile validation purposes and miR quantitation in patient SFs. Dysregulated miR target genes and pathways were predicted via bioinformatic algorithms. Overall design: Synovial Fibroblasts isolated from TghuTNF mice (2 x biological replicates) and control WT littermate mice (2 x biological replicates)
Publication Title
Identification of microRNA-221/222 and microRNA-323-3p association with rheumatoid arthritis via predictions using the human tumour necrosis factor transgenic mouse model.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gata2 dependent genes in mouse uteri were identified by the conditional ablation of Gata2 using the (PR-cre) mouse upon acute progesterone administration.
Publication Title
A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples