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SRP159572
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2500
Description
Progenitors of the first hematopoietic cells in the mouse arise in the early embryo from Brachyury-positive multipotent cells in the posterior-proximal region of the epiblast, but the mechanisms that specify primitive blood cells are still largely unknown. Pluripotency factors maintain uncommitted cells of the blastocyst and embryonic stem cells in the pluripotent state. However, little is known about the role played by these factors during later development, despite their being expressed in the postimplantation epiblast. Using a dual transgene system for controlled expression at postimplantation stages, we found that Nanog blocks primitive hematopoiesis in the gastrulating embryo, resulting in a loss of red blood cells and downregulation of erythropoietic genes. Accordingly, Nanog deficient embryonic stem cells are prone to erythropoietic differentiation. Moreover, Nanog expression in adults prevents the maturation of erythroid cells. By analysis of previous data for NANOG binding during stem cell differentiation and CRISPR/Cas9 genome editing, we found that Tal1 is a direct NANOG target. Our results show that Nanog regulates primitive hematopoiesis by directly repressing critical erythroid lineage specifiers. Overall design: MEPs mRNA profiles of adult mice Nanog-tg treated and untreated with doxycycline were generated by deep sequencing, in triplicate, using Illumina GAIIx.
Publication Title
The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates <i>Tal1</i>.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In an accompanying paper we found specific localization of diabetogenic T cells only to islets of Langerhans bearing the specific antigen. Instrumental in the specific localization was the presence of intra-islet dendritic cells bearing the -cell-peptide-MHC complex. Here we report that the entry of diabetogenic CD4 T cells very rapidly triggered inflammatory gene expression changes in islets and vessels by up-regulating chemokines and adhesion molecules. VCAM-1 expression was notable in blood vessels and so was ICAM-1. ICAM-1 was also found on -cells. These expression changes induced the entry of non-specific T cells that otherwise did not localize to the islets. In contrast to the entry of diabetogenic CD4 T cells, the entrance of non-specific T cells required a chemokine response and VCAM-1 expression by the islets. Interferon-gamma was important for the early gene expression changes in the islets. By microarray analysis we detected up-regulation of a group of interferon-inducible genes as early as 8 hours post T cell transfer. These studies provide a baseline to examine the development of therapeutics that can modulate islet localization of diabetogenic T cells to control this autoimmune disease.
Publication Title
Entry of diabetogenic T cells into islets induces changes that lead to amplification of the cellular response.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
p63 is critical for epithelial development yet little is known about the transcriptional programmes it regulates. The p63 transactivating (TA) isoforms contain an amino-terminal exon that encodes a p53-like transactivation domain, whereas N-isoforms lack this domain but contain the common DNA binding domain (DBD), suggesting that TAp63 and Np63 isoforms may have opposing functions. By characterising transcriptional changes and cellular effects following modulation of p63 expression, we have defined a vital role for p63 in cellular adhesion. Knockdown of p63 expression caused downregulation of cell adhesion-associated genes, cell detachment and anoikis in mammary epithelial cells and keratinocytes. Conversely, overexpression of the TAp63 or Np63 isoforms of p63 upregulated cell adhesion molecules, increased cellular adhesion and conferred resistance to anoikis.
Publication Title
p63 regulates an adhesion programme and cell survival in epithelial cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to unveil the gene expression alterations upon short-term HFD administration
Publication Title
Dietary alterations modulate susceptibility to Plasmodium infection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 57 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Type 1 diabetes (T1D) is an autoimmune disease triggered by T cell reactivity to protein antigens produced by the -cells. Here we present a chronological compendium of transcriptional profiles from islets of Langerhans isolated from non-obese diabetic (NOD) mice ranging from 2 wks up to diabetes and compared to controls. Parallel analysis was made of cellular components of the islets. Myeloid cells populated the islets early during development in all mouse strains. This was followed by a type I interferon signature detectable at 4-6 wks of age only in diabetes susceptible mice. Concurrently, CD4 T cells were found within islets, many in contact with intra-islet antigen presenting cells. Early cellular signs of islet reactivity were detected by six wks. By 8 wks, NOD islets contained all major leukocytes populations and an inflammatory gene signature. This work establishes the natural transcriptional signature of T1D and provides a resource for future research.
Publication Title
Defining the transcriptional and cellular landscape of type 1 diabetes in the NOD mouse.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
MM1.S cells stably transduced with control or b-catenin shRNA were established. Total RNA was isolated from 5x 10^6 cells of each in triplicate.
Publication Title
Aurora kinase A is a target of Wnt/beta-catenin involved in multiple myeloma disease progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 46 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
Numerous studies have shown the potential of spermatozoal RNAs to delineate failures of spermatogenic pathways in infertile samples. However, the RNA contribution of normal fertile samples still needs to be established in relation to transcripts consistently present in human spermatozoa. We report here the spermatozoal transcript profiles characteristic of 24 normally fertile individuals. RNA was extracted from the purified sperm cells of ejaculate and hybridized to Illumina Human-8 BeadChip Microarrays
Publication Title
Identification of human sperm transcripts as candidate markers of male fertility.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 27 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
NOD mice deficient in the transcription factor Batf3 never develop diabetes. The goal of this study was to determine if NOD.Batf3-/- mice islets had any inflammatory signature associated with type 1 diabetes. Islets of Langerhans were isolated from NOD, NOD.Batf3-/-, and NOD.Rag1-/- and then compared to determine inflammatory gene profiles. At 6 and 8 weeks of age, NOD.Batf3-/- islets had an absence of inflammatory gene expression and were almost identical to uninflamed NOD.Rag1-/- islets. This work shows that absence of the Batf3 transcription factor is sufficient to prevent all the inflammatory sequelae of autoimmune diabetes.
Publication Title
A minor subset of Batf3-dependent antigen-presenting cells in islets of Langerhans is essential for the development of autoimmune diabetes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 1000
Description
Carbon nanotubes (CNTs) are fibrous particulates made up of elemental carbon and a novel nanomaterial known for its variety of industrial applications. It has been shown that lung exposure to CNTs may cause adverse effects inclunding lung inflammation and remodeling in experimental models. We investigated the impact of genetic background on the development of adverse outcomes by comparing several common inbred mouse strains and found that C57Bl/6 and DBA/2 strains were polarized in their sensitivity to adverse changes at 4 weeks following an exposure to 4 mg/kg CNT. Here we compare underlying gene expression profiles which may inform the understanding of lung biology underpinning genetic susceptibility to adverse outcomes following environmental or occupational exposure to CNTs. Overall design: Changes in mRNA profiles were compared between CNT-exposed animals and vehicle-treated controls (n=3/group) of either C57Bl/6 or DBA/2 strains.
Publication Title
Genetic susceptibility to toxicologic lung responses among inbred mouse strains following exposure to carbon nanotubes and profiling of underlying gene networks.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 33 Downloadable Samples
- Illumina HiSeq 2500
Description
We examined the transcriptional profiles of macrophages that reside in the islets of Langerhans of NOD, NOD.Rag1-/-, and B6.g7 mice at three weeks of age. Islet macrophages expressed an activation signature with high expression of Tnf, Il1b, and MHC-II both at the transcript and protein levels. These features are common with barrier macrophages of the lung and gastrointestinal tract. Moreover, injection of lipopolysaccharide induced a rapid inflammatory gene expression, indicating that blood stimulants are accessible to the macrophages and that these macrophages can sense them. In NOD mice, the autoimmune process imparted an increased inflammatory signature, including elevated expression of chemokines, chemokine receptors, and an oxidative response. The elevated inflammatory signature indicates that the autoimmune program was active at the time of weaning. Thus, the macrophages of the islets of Langerhans are poised to mount an immune response even at steady state, while the presence of the adaptive immune system elevates their activation state. Overall design: We examined the transcriptional profiles of macrophages that reside in the islets of Langerhans of NOD, NOD.Rag1-/-, and B6.g7 mice at three weeks of age. Lung macrophages and pancreatic LN dendritic cells of NOD mice were also examined.
Publication Title
The islet-resident macrophage is in an inflammatory state and senses microbial products in blood.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples