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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- 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- Homo sapiens
- 14 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Samples collected from human subjects in clinical trials possess a level of complexity, arising from multiple cell types, that can obfuscate the analysis of data derived from them. Blood, for example, contains many different cell types that are derived from a distinct lineage and carry out a different immunological purpose. Failure to identify, quantify, and incorporate sources of heterogeneity into an analysis can have widespread and detrimental effects on subsequent statistical studies.
Publication Title
Optimal deconvolution of transcriptional profiling data using quadratic programming with application to complex clinical blood samples.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 59 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
A clinical study evaluating the dosing of an oral HDACi panobinostat in patient infected with HIV-1. Dosing was 20 mg orally, 3 times weekly, every other week for a total of 8 weeks.
Publication Title
Treatment of HIV-Infected Individuals with the Histone Deacetylase Inhibitor Panobinostat Results in Increased Numbers of Regulatory T Cells and Limits <i>Ex Vivo</i> Lipopolysaccharide-Induced Inflammatory Responses.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 47 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Vaccine research today is focused on using safer, highly purified or recombinant antigens with poor immunogenicity, which has created a need for potent adjuvants. Rational design of effective and safe mucosal adjuvants for human use necessitates a thorough understanding of the mode of action of successful candidate adjuvants.
Publication Title
Unraveling molecular signatures of immunostimulatory adjuvants in the female genital tract through systems biology.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
ABSTRACT
Publication Title
Bone marrow-derived macrophages from BALB/c and C57BL/6 mice fundamentally differ in their respiratory chain complex proteins, lysosomal enzymes and components of antioxidant stress systems.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Schwann cell maturation is tightly controlled by a set of transcriptional regulators. We have deleted the zinc-finger transcription factor Sip1 specifically from immature Schwann cells and observed a dramatic developmental delay.
Publication Title
Zeb2 is essential for Schwann cell differentiation, myelination and nerve repair.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Affymetrix HG U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA) was used to profile transcriptomes and discover altered gene expression in saliva supernatant. Salivary transcriptomic biomarker discovery was performed on 10 lung cancer patients and 10 matched controls.
Publication Title
Development of transcriptomic biomarker signature in human saliva to detect lung cancer.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mycobacteria-induced apoptosis of macrophages plays an important role in modulation of the host immune response involving TNF-alpha as major cytokine. The underlying mechanisms are still ill-defined. Here, we show for the first time that methylglyoxal (MG) and AGEs levels were elevated during mycobacterial infection of macrophages and that their increased levels mediated mycobacteria-induced apoptotic and immune response of macrophages. Moreover, we show that high levels of AGEs were formed at the sites of pulmonary tuberculosis. This observation represents the first evidence of the potential involvement of AGEs in tuberculosis and in infectious diseases in general. Global gene expression profiling of MG-treated macrophages reveals diversified potential roles of MG in cellular processes, including apoptosis, immune response, and growth regulation. The results of this study provide new insights into intervention strategies to develop therapeutic tools against infectious diseases in which MG and AGE production plays critical roles.
Publication Title
Critical role of methylglyoxal and AGE in mycobacteria-induced macrophage apoptosis and activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Insight into mechanisms controlling gene expression in the spermatogonial stem cell (SSC) will improve our understanding of the processes regulating spermatogenesis and aid in treating problems associated with male infertility.
Publication Title
Spermatogonial stem cell self-renewal requires ETV5-mediated downstream activation of Brachyury in mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples