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GSE16983
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- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Epigenetic modifications must underlie lineage-specific differentiation since terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Hematopoiesis provides a well-defined model of progressive differentiation in which to study the role of epigenetic modifications in cell fate decisions. Multi-potent progenitors (MPPs) can differentiate into all blood cell lineages, while downstream progenitors commit to either myeloerythroid or lymphoid lineages. While DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs {Broske, 2009 #6}, a comprehensive DNA methylation map of hematopoietic progenitors, or of any cell lineage, does not exist. Here we have generated a mouse DNA methylation map, examining 4.6 million CpG sites throughout the genome including all CpG islands and shores, examining MPPs, all lymphoid progenitors (ALPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Interestingly, differentiation towards the myeloid lineage corresponds with a net decrease in DNA methylation, while lymphoid commitment involves a net increase in DNA methylation, but both show substantial dynamic changes consistent with epigenetic plasticity during development. By comparing lineage-specific DNA methylation to gene expression array data, we find many examples of genes and pathways not previously known to be involved in lymphoid/myeloid differentiation, such as Gcnt2, Arl4c, Gadd45, and Jdp2. Several transcription factors, including Meis1 and Prdm16 were methylated and silenced during differentiation, suggesting a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome appears to be important in hematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation, often correlating with gene expression changes, and define a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions.
Publication Title
Comprehensive methylome map of lineage commitment from haematopoietic progenitors.
Sample Metadata Fields
Sex, Age
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
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Brain-derived serotonin favors appetite in mice following its binding to the Htr1a and Htr2b receptors in arcuate neurons of the hypothalamus. In this study, we identified that CREB is the transcriptional effector of brain-derived serotonin control of appetite in arcuate nuclei.
Publication Title
Leptin-dependent serotonin control of appetite: temporal specificity, transcriptional regulation, and therapeutic implications.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 1000
Description
Epithelial-neuronal signaling is essential for sensory encoding in touch, itch and nociception; however, little is known about the release mechanisms and neurotransmitter receptors through which skin cells govern neuronal excitability. Merkel cells are mechanosensory epidermal cells that have long been proposed to activate neuronal afferents through chemical synaptic transmission. We employed a set of classical criteria for chemical neurotransmission as framework to directly test this hypothesis. RNA sequencing of adult Merkel cells demonstrated that they express presynaptic molecules and biosynthetic machinery for adrenergic transmission. Moreover, live-cell imaging directly demonstrated that Merkel cells mediate activity- and VMAT-dependent release of fluorescent catecholamine neurotransmitter analogues. Touch-evoked firing in Merkel-cell afferents was inhibited either by pre-synaptic silencing of SNARE-mediated vesicle release from Merkel cells or by neuronal deletion of b2-adrenergic receptors. Together, these results identify both pre- and postsynaptic mechanisms through which Merkel cells excite mechanosensory afferents to encode gentle touch. Overall design: RNA-seq of basal keratinocytes and Merkel cells purified with FACS
Publication Title
Merkel Cells Activate Sensory Neural Pathways through Adrenergic Synapses.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples