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SRP067686
Mus musculus
20 Downloadable Samples
Illumina HiSeq 2000
Description
The first HSCs are produced in the aorta-gonadmesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. BMP4 and Hedgehog affect their production/expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smad-activated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture. Overall design: Embryonic day 11 AGM are dissected and either analyzed directly, or after explant culture in conditions containing BMP/Hedgehog with or without cyclopamine. EC: endothelial enriched (CD31+Kit-); MC: mesenchymal cell enriched (CD31-Kit-); HPSC: hematopoietic progenitor/stem cell enriched; AGM11: E11 fresh AGMs; AGMex: AGM after explant culture; AGMcy: AGM after explant in presence of cyclopamine; CD31p: CD31 positive; CD31n: CD31 negative; KITp: c-Kit positive; KITn: c-Kit negative; BREp: BRE-GFP positive; BREn: BRE-GFP negative
Publication Title
BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Parathyroid hormone (PTH) plays an essential role in regulating calcium and bone homeostasis in the adult, but whether PTH is required at all for regulating fetal-placental mineral homeostasis is uncertain. To address this we treated Pth-null mice in utero with 1 nmol PTH (1-84) or saline and examined placental calcium transfer 90 minutes later. It was found that placental calcium transfer increased in Pth-null fetuses treated with PTH as compared to Pth-null fetuses treated with saline. Subsequently, to determine the effect of PTH treatment on placental gene expression, in a separate experiment, 90 minutes after the fetal injections the placentas were removed for subsequent RNA extraction and microarray analysis.
Publication Title
Parathyroid hormone regulates fetal-placental mineral homeostasis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is generally unresponsive to therapy. African Americans have an increased risk for esophageal squamous cell cancer (ESCC), the subtype that shows marked variation in geographic frequency. To identify key genes involved in ESC carcinogenesis in African Americans we conducted microarray expression profiling and found a significant dysregulation of genes encoding stress response and drug-metabolizing enzymes, mainly in NRF2 pathway. The involvement of NRF2 mediated oxidative damage represent a key step in the evolution of African American ESCC. Loss of activity of these enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence of ESCC in this ethnic group. The differential expression profile also indicates an inflammatory component and tissue regeneration in ESCC tumorigenesis. Together, these findings suggest a remarkable interplay of genetic and environmental factors in the pathogenesis of African American ESCC.
Publication Title
African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks.
Sample Metadata Fields
Race
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina Genome Analyzer
Description
Prospective isolation is critical to understand the cellular and molecular aspects of stem cell heterogeneity. Here we identify the cell surface antigen CD9 as a novel positive marker that provides a simple alternative for hematopoietic stem cell-isolation at high purity Overall design: mRNA profiles of LT and ST HSCs
Publication Title
The tetraspanin CD9 affords high-purity capture of all murine hematopoietic stem cells.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 78 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Type I IFNs are implicated in the pathophysiology of systemic sclerosis (SSc). Recently, a Phase I open-label trial was conducted with an anti-IFNAR1 receptor antibody (anifrolumab) in adult SSc patients. In this study, we aim to assess the downstream effects of anifrolumab and elucidate the role of type I IFN in SSc. Serum proteins and extracellular matrix (ECM) markers were measured in relation to IFN pathway activation status and SSc disease activity. Our results demonstrated a robust overexpression of multiple serum proteins in SSc patients, particularly those with an elevated baseline type I IFN gene signature. Anifrolumab administration was associated with significant downregulation of T cellassociated proteins and upregulation of type III collagen degradation marker. Whole-blood and skin microarray results also indicated the inhibition of T cell receptor and ECMrelated transcripts by anifrolumab. In summary, our study demonstrates suppressive effects of anifrolumab on T cell activation and collagen accumulation through which tissue fibrosis may be reduced in SSc patients. The relationship between these peripheral markers and the clinical response to anifrolumab may be examined in larger double-blind, placebo-controlled trials.
Publication Title
Suppression of T Cell Activation and Collagen Accumulation by an Anti-IFNAR1 mAb, Anifrolumab, in Adult Patients with Systemic Sclerosis.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Time
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Skeletal muscle mass is an important determinant of whole-body glucose disposal. We here show that mice (M-PDK1KO mice) with skeletal muscle–specific deficiency of 3'-phosphoinositide–dependent kinase 1 (PDK1), a key component of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, manifest a reduced skeletal muscle mass under the static condition as well as impairment of exercise load–induced muscle hypertrophy.
Publication Title
Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Most tumors are epithelial-derived, and although disruption of polarity and aberrant cellular junction formation is a poor prognosticator in human cancer, the role of polarity determinants in oncogenesis is poorly understood. Using in vivo selection, we identified a mammalian orthologue of the Drosophila polarity regulator crumbs as a gene whose loss of expression promotes tumor progression. Immortal baby mouse kidney epithelial (iBMK) cells selected in vivo to acquire tumorigenicity displayed dramatic repression of crumbs3 (crb3) expression associated with disruption of tight junction formation, apicobasal polarity, and contact-inhibited growth. Restoration of crb3 expression restored junctions, polarity and contact inhibition, while suppressing migration and metastasis. These findings suggest a role for mammalian polarity determinants in suppressing tumorigenesis that may be analogous to the well-studied polarity tumor suppressor mechanisms in Drosophila.
Publication Title
Role of the polarity determinant crumbs in suppressing mammalian epithelial tumor progression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To discover novel growth factors for hematopoietic stem- and progenitor cells (HSPCs), we have assessed cytokine responses of cord blood (CB)-derived CD34+ cells in a high-content growth factor screen. We identify the immunoregulatory chemokine (C-C motif) ligand 28 (CCL28) as a novel growth factor that directly stimulates proliferation of primitive hematopoietic cells from different ontogenetic origins.
Publication Title
Identification of the chemokine CCL28 as a growth and survival factor for human hematopoietic stem and progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina Genome Analyzer
Description
Malformations of the cardiovascular system are the most common type of birth defect in humans, affecting predominantly the formation of valves and septa. During heart valve and septa formation, cells from the atrio-ventricular canal (AVC) and outflow tract (OFT) regions of the heart undergo an epithelial-to-mesenchymal transformation (EMT) and invade the underlying extracellular matrix to give rise to endocardial cushions. Subsequent maturation of newly formed mesenchyme cells leads to thin stress-resistant leaflets. TWIST1 is a basic helix-loop-helix transcription factor expressed in newly formed mesenchyme cells of the AVC and OFT that has been shown to play roles in cell survival, cell proliferation and differentiation. However, the role and downstream targets of TWIST1 during heart valve formation remain unclear. To identify genes important for heart valve development downstream of Twist1 we performed global gene expression profiling of AVC, OFT, atria and ventricles of the embryonic day 10.5 mouse heart by tag-sequencing (Tag-seq). Using this resource we identified a novel set of 1246 genes, including 201 regulators of transcription, enriched in the valve forming regions of the heart. We compared these genes to a Tag-seq library from the Twist1 null developing valves revealing significant gene expression changes. These changes were consistent with a role of TWIST1 in controlling differentiation of mesenchymal cells following their transformation from endothelium in the mouse. To study the role of TWIST1 at the DNA level we performed chromatin immunoprecipitation and identified novel direct targets of TWIST1 in the developing heart valves. Our findings are consistent with a role for TWIST1 in the differentiation of AVC mesenchyme post-EMT in the mouse, and suggest that TWIST1 exerts its function by direct DNA binding to activate valve specific gene expression. Overall design: Profiled the AVC, OFT, atria and ventricles of the embryonic day 10.5 mouse heart by tag-sequencing (Tag-seq) (no replicates). We also produced a Tag-seq library from Twist1 null developing valves to reveal the gene expression changes associated with loss of this gene.
Publication Title
Twist1 transcriptional targets in the developing atrio-ventricular canal of the mouse.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Lysosomal cathepsins regulate an exquisite range of biological functions, and their deregulation is associated with inflammatory, metabolic and degenerative disease in humans. Here, we identified a key cell-intrinsic role for cathepsin B as a negative feedback regulator of lysosomal biogenesis and autophagy. Mice and macrophages lacking cathepsin B activity had increased resistance to the cytosolic bacterial pathogen Francisella novicida. Genetic deletion or pharmacological inhibition of cathepsin B downregulated mTOR activity and prevented cleavage of the lysosomal calcium channel TRPML1. These events drove transcription of lysosomal and autophagy genes via the transcription factor TFEB, which increased lysosomal biogenesis and activation of autophagy-initiation kinase ULK1 for clearance of the bacteria. Our results identified a fundamental biological function of cathepsin B in providing a checkpoint for homeostatic maintenance of lysosome population and basic recycling functions in the cell.
Publication Title
Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection.
Sample Metadata Fields
Specimen part
View Samples