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SRP055082
Mus musculus
8 Downloadable Samples
Illumina Genome Analyzer II
Description
TAR DNA-binding protein 43 (TDP-43) is normally a nuclear RNA-binding protein that exhibits a range of functions including regulation of alternative splicing, RNA trafficking and RNA stability. However, in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), TDP-43 is abnormally phosphorylated, ubiquitinated, and cleaved, and is mislocalized to the cytoplasm where it forms distinctive aggregates. We previously developed a mouse model expressing human TDP-43 with a mutation in its nuclear localization signal (?NLS-hTDP-43) so that the protein preferentially localizes to the cytoplasm. These mice did not exhibit a significant number of cytoplasmic aggregates, but did display a loss of endogenous mouse nuclear TDP-43 as well as dramatic changes in gene expression as measured by microarray. Here, we analyze RNA-sequencing data from the ?NLS-hTDP-43 mouse model, together with published RNA-sequencing data obtained previously from TDP-43 antisense oligonucleotide (ASO) knockdown mice and High Throughput Sequencing of RNA isolated by CrossLinking ImmunoPrecipitation (HITS-CLIP) data of TDP-43’s RNA binding targets to further investigate the dysregulation of gene expression in the ?NLS model. This analysis reveals that the transcriptomic effects of the overexpression of the ?NLS-hTDP-43 transgene are likely due to a gain of cytoplasmic function. Moreover, cytoplasmic TDP-43 expression alters transcripts that regulate chromatin assembly, the nucleolus, lysosomal function, and histone 3’ untranslated region (UTR) processing. These transcriptomic alterations correlate with observed histologic abnormalities in heterochromatin structure and nuclear size in transgenic mouse and human brains. Overall design: RNAseq of bigenic (n=4) ?NLS-hTDP-43 and control nontransgenic (n=4) mouse cortex
Publication Title
Transcriptomic Changes Due to Cytoplasmic TDP-43 Expression Reveal Dysregulation of Histone Transcripts and Nuclear Chromatin.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Primary murine osteoblasts were isolated form the calvariae of newborn mice. 10 days after the addition of ascorbic acid (50 g/ml) and -glycerophosphate (10 mM), cells were serum-starved over night and then incubated for 6 hours with condtioned medium of MDA-PCa2b cells or conditioned medium of PC-3 cells
Publication Title
Osteolytic prostate cancer cells induce the expression of specific cytokines in bone-forming osteoblasts through a Stat3/5-dependent mechanism.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Genome-wide comparative gene expression analysis of callus tissue of osteoporotic mice (Col1a1-Krm2 and Lrp5-/-) and wild-type were performed to identify candidate genes that might be responsible for the impaired fracture healing observed in Col1a1-Krm2 and Lrp5-/- mice.
Publication Title
Osteoblast-specific Krm2 overexpression and Lrp5 deficiency have different effects on fracture healing in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
DLK1/FA-1 (delta-like 1/fetal antigen-1) is a transmembrane protein belonging to Notch/Delta family that acts as a membrane-associated or a soluble protein to regulate regeneration of a number of adult tissues. Here, we examined the role of DLK1/FA-1 in bone biology using osteoblast-specific-Dlk1 over-expressing mice (Col1-Dlk1). Col1-Dlk1 mice displayed growth retardation and significantly reduced total body weight and bone mineral density (BMD). CT-scanning revealed a reduced trabecular and cortical bone volume fraction. Tissue-level histomorphometric analysis demonstrated decreased bone formation rate and enhanced bone resorption in Col1-Dlk1 as compared to WT. At a cellular level, DLK1 markedly reduced the total number of bone marrow (BM)-derived CFU-F, as well as their osteogenic capacity. In a number of in vitro culture systems, DLK1 stimulated osteoclastogenesis indirectly through osteoblast-dependent increased production of pro-inflammatory bone resorbing cytokines (e.g, Il7, Tnfa and Ccl3). We found that ovariectomy (ovx)-induced bone loss was associated with increased production of DLK1 in bone marrow by activated T-cells. However, Dlk1-/- mice were protected from ovx-induced bone loss. Thus, we identified DLK1 as a novel regulator of bone mass that function to inhibit bone formation and to stimulate bone resorption. Increasing DLK1 production by T-cells under estrogen deficiency suggests its possible use as a therapeutic target for preventing postmenopausal bone loss.
Publication Title
DLK1 is a novel regulator of bone mass that mediates estrogen deficiency-induced bone loss in mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the present study we analyzed the effect of primary osteoporosis and advanced donor age on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from bone marrow. Human MSC of elderly patients suffering from osteoporosis were isolated from femoral heads after low-energy fracture of the femoral neck. Control cells were obtained from bone marrow of femoral heads of middle-aged, non-osteoporotic donors after total hip arthroplasty.
Publication Title
The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the present study we analyzed the effect of cellular senescence on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from bone marrow. Human MSC were isolated from femoral heads of non-osteoporotic donors after total hip arthroplasty.
Publication Title
The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the present study we analyzed the effect of primary osteoporosis on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from human bone marrow. Human MSC of elderly patients suffering from osteoporosis were isolated from femoral heads after low-energy fracture of the femoral neck. Bone marrow of age-matched, non-osteoporotic donors was obtained of femoral heads after total hip arthroplasty.
Publication Title
The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the present study we analyzed the effect of advanced donor age on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from bone marrow. Human MSC of elderly and middle-aged patients without symptoms of osteoporosis were isolated from femoral heads after total hip arthroplasty.
Publication Title
The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Sus scrofa
- 6 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
The aim of the current study was to identify molecular markers for articular cartilage that can be used for the quality control of tissue engineered cartilage. Therefore a genom-wide expression analysis was performed using RNA isolated from articular and growth plate cartilage, both extracted from the knee joints of minipigs.
Publication Title
Identification of molecular markers for articular cartilage.
Sample Metadata Fields
Specimen part
View Samples