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SRP040645
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2500
Description
Proximal spinal muscular atrophy (SMA) is an early onset, autosomal recessive motor neuron disease caused by loss of or mutation in SMN1 (survival motor neuron 1). Despite understanding the genetic basis underlying this disease, it is still not known why motor neurons (MNs) are selectively affected by the loss of the ubiquitously expressed SMN protein. Using a mouse embryonic stem cell (mESC) model for severe SMA, the RNA transcript profiles (transcriptomes) between control and severe SMA (SMN2+/+;mSmn-/-) mESC-derived MNs were compared in this study using massively parallel RNA sequencing (RNA-Seq). The MN differentiation efficiencies between control and severe SMA mESCs were similar. RNA-Seq analysis identified 3094 upregulated and 6964 downregulated transcripts in SMA mESC-derived MNs when compared against control cells. Pathway and network analysis of the differentially expressed RNA transcripts showed that pluripotency and cell proliferation transcripts were significantly increased in SMA MNs while transcripts related to neuronal development and activity were reduced. The differential expression of selected transcripts such as Crabp1, Crabp2 and Nkx2.2 was validated in a second mESC model for SMA as well as in the spinal cords of low copy SMN2 severe SMA mice. Furthermore, the levels of these selected transcripts were restored in high copy SMN2 rescue mouse spinal cords when compared against low copy SMN2 severe SMA mice. These findings suggest that SMN deficiency affects processes critical for normal development and maintenance of MNs. Overall design: RNA profiles were generated from FACS-purified control and SMA mESC-derived motor neurons (n=3/genotype) by deep sequencing using Illumina HighSeq 2500
Publication Title
Transcriptome profiling of spinal muscular atrophy motor neurons derived from mouse embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 6 Downloadable Samples
Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Topoisomerase 1 (TOP1) poisons like camptothecin (CPT), which are used as chemotherapeutic agents in cancer, elicit DNA damage in quiescient neurons. In this study, we examined the effects of CPT and actinomycin D (ActD) on neuronal cells. Motor (MNs) and cortical (CNs) neurons were more susceptible to the toxic effects of CPT and ActD than fibroblasts. MNs and CNs exhibited a delayed DNA damage responseincrease in nuclear -H2AX focirelative to fibroblasts. Neuronal cells expressed higher levels of Top1 mRNA than fibroblasts which could explain their enhanced vulnerability to CPT and ActD toxicity. Microarray analysis was performed to identify differentially regulated transcripts in MNs treated with CPT for 2 hours. Many immediate-early genes including Fos and Egr-1 were upregulated in CPT-treated MNs. Fos mRNA levels were elevated in all cells types treated with CPT; Egr-1 transcript levels, however, were reduced in CPT-treated fibroblasts even though they were elevated in treated MNs and CNs. Pathway and network analysis of the differentially expressed transcripts revealed activation of ERK and JNK signaling cascades in CPT-treated MNs. In conclusion, MNs were more vulnerable than fibroblasts to the damaging effects of TOP1 poisons and they elicit a unique intracellular response to CPT treatment.
Publication Title
Identification of early gene expression changes in primary cultured neurons treated with topoisomerase I poisons.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This file contains gene microarray data from bone marrow pre-ul DC, in vitro derived CD103+CD11b+ and CD103+CD11b- cDC with or without retinoic acid.
Publication Title
Generation and transcriptional programming of intestinal dendritic cells: essential role of retinoic acid.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Anagrelide is a cytoreductive agent used to lower platelet counts in essential thrombocythemia. Although the drug is known to selectively inhibit megakaryopoiesis, the molecular mechanism accounting for this activity has not been elucidated.
Publication Title
The gene expression signature of anagrelide provides an insight into its mechanism of action and uncovers new regulators of megakaryopoiesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Alveolar soft-part sarcoma (ASPS) is an extremely rare, highly vascular soft tissue sarcoma affecting predominantly adolescents and young adults. In an attempt to gain insight into the pathobiology of this enigmatic tumor, we performed the first genome-wide gene expression profiling study.
Publication Title
Gene expression profiling of alveolar soft-part sarcoma (ASPS).
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human naive T cells from peripheral blood were cultured in 24 wells coated with anti-CD3 and anti-CD28 antibodies in the presence or absence of retinoid acid, IL-12, and 1,25 (OH)2 vitamin D3. The T cells were FACS-sorted based on expression of CD3, integrin alpha4beta7, cutaneous lymphocyte antigen (CLA) and chemokine receptor 10. This serie includes microarray data from stimulated T cells under indicated conditions.
Publication Title
DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 2 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Two major subsets of rat natural killer (NK) cells can be distinguished based on their expression of either the Ly49s3 or the NKR-P1B lectin-like receptor. Ly49s3+ NK cells, but not NKR-P1B+ NK cells, express a wide range of Ly49 receptors.
Publication Title
Two complementary rat NK cell subsets, Ly49s3+ and NKR-P1B+, differ in phenotypic characteristics and responsiveness to cytokines.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This file contains gene microarray data from FACS purified mouse high endothelial cells and capillary endothelial cells from peripheral lymph nodes, mesenteric lymph nodes, and Peyers patches. The data will allow for better understanding of the specialization of high endothelial venules (HEV) and their role in lymphocyte recruitment from the blood; the tissue-specific differentiation of lymphoid tissue vasculature; and the specialized features of capillary vs. post-capillary endothelium, including differences in signaling pathways, adhesive properties and mechanisms of hemostasis.
Publication Title
Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Aging is a progressive process that results in the accumulation of intra- and extracellular alterations that in turn contribute to a reduction in health. Age-related changes in DNA methylation have been reported before and may be responsible for aging-induced changes in gene expression, although a causal relationship has yet to be shown. Using genome-wide assays, we analyzed age-induced changes in DNA methylation and their effect on gene expression with and without transient induction with the synthetic transcription modulating agent WY14,643. To demonstrate feasibility of the approach, we isolated peripheral blood mononucleated cells (PBMCs) from five young and five old healthy male volunteers and cultured them with or without WY14,643. Infinium 450K BeadChip and Affymetrix Human Gene 1.1 ST expression array analysis revealed significant differential methylation of at least 5 % (YO>5 %) at 10,625 CpG sites between young and old subjects, but only a subset of the associated genes were also differentially expressed. Age-related differential methylation of previously reported epigenetic biomarkers of aging including ELOVL2, FHL2, PENK, and KLF14 was confirmed in our study, but these genes did not display an age-related change in gene expression in PBMCs. Bioinformatic analysis revealed that differentially methylated genes that lack an age-related expression change predominantly represent genes involved in carcinogenesis and developmental processes, and expression of most of these genes were silenced in PBMCs. No changes in DNA methylation were found in genes displaying transiently induced changes in gene expression. In conclusion, aging-induced differential methylation often targets developmental genes and occurs mostly without change in gene expression.
Publication Title
Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject
View Samples