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GSE594
Rattus norvegicus
54 Downloadable Samples
Affymetrix Rat Genome U34 Array (rgu34a)
Description
mRNA gene expression was measured in intact female Sprague-Dawley rats at 6 (young), 26 (adult) and 52 (older) weeks of age at the time of fracture. Samples were collected at 0, 0.4, 1, 2, 4, and 6 weeks after fracture. RNA from two rats were pooled for each Affymetrix Rat U34A array. Mid-shaft, simple, transverse left femoral fractures were induced after retrograde intramedullary rod fixation with a Bonnarens and Einhorn device. Samples were collected from one third of the femoral length, centered on the fracture site, including the external callus, cortical bone, and marrow elements.
Publication Title
Altered mRNA expression of genes related to nerve cell activity in the fracture callus of older rats: A randomized, controlled, microarray study.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
mRNA gene expression was measured in rats at 6 (young), 26 (adult) and 52 (older) weeks of age at the time of fracture. Samples were collected at 0, 0.4, 1, 2, 4, and 6 weeks after fracture. RNA from two rats were pooled for each Affymetrix Rat U34A array.
Publication Title
Altered mRNA expression of genes related to nerve cell activity in the fracture callus of older rats: A randomized, controlled, microarray study.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Study of rat femur fracture healing in young (6 weeks old), adult (26 weeks old), and older (52 weeks old) rats with samples collected at 0 time (no fracture) and at 0.4, 1, 2, 4, and 6 weeks after fracture. RNA from two rats were pooled for each array.
Publication Title
Altered mRNA expression of genes related to nerve cell activity in the fracture callus of older rats: A randomized, controlled, microarray study.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Mid-shaft fracture stimulates bone lengthening by increasing linear growth at the growthplate. This project studied changes in mRNA in the proximal growthplate after a mid-shaft fracture in a rat model.
Publication Title
Evidence for overgrowth after midfemoral fracture via increased RNA for mitosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
mRNA used for the analysis of these microarrays were previously analyzed for 34 genes by reverse transcription - polymerase chain reaction in Desai BJ et al., J.Orthop.Trauma 17: 689-698, 2003. These two data sets were subsequently studied to compare the results from these two different methods for mRNA quantitation. The comparison was publised in "Comparison of mRNA gene expression by RT-PCR and DNA microarray" by W. Etienne, M.H. Meyer, J. Peppers, and R.A. Meyer, Jr., BioTechniques 36 (4): 618-626, April 2004.
Publication Title
Comparison of mRNA gene expression by RT-PCR and DNA microarray.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 29 Downloadable Samples
Illumina HiSeq 2000
Description
To achieve the extreme nuclear condensation necessary for sperm function, most histones are replaced with protamines during spermiogenesis in mammals. Mature sperm retain only a small fraction of nucleosomes, which are, in part, enriched on gene regulatory sequences, and recent findings suggest that these retained histones provide epigenetic information that regulates expression of a subset of genes involved in embryo development after fertilization. We addressed this tantalizing hypothesis by analyzing two mouse models exhibiting abnormal histone positioning in mature sperm due to impaired poly(ADP-ribose) (PAR) metabolism during spermiogenesis and identified altered sperm histone retention in specific gene loci genome-wide using MNase digestion-based enrichment of mononucleosomal DNA. We then set out to determine the extent to which expression of these genes was altered in embryos generated with these sperm. For control sperm, most genes showed some degree of histone association, unexpectedly suggesting that histone retention in sperm genes is not an all-or-none phenomenon and that a small number of histones may remain associated with genes throughout the genome. The amount of retained histones, however, was altered in many loci when PAR metabolism was impaired. To ascertain whether sperm histone association and embryonic gene expression are linked, the transcriptome of individual 2-cell embryos derived from such sperm was determined using microarrays and RNA sequencing. Strikingly, a moderate but statistically significant portion of the genes that were differentially expressed in these embryos also showed different histone retention in the corresponding gene loci in sperm of their fathers. These findings provide new evidence for the existence of a linkage between sperm histone retention and gene expression in the embryo. Overall design: 9 WT samples in 3 groups of 3. Each group consists of 3 eggs fertilized by the same father. 9 KO samples in the same setup.
Publication Title
Paternal poly (ADP-ribose) metabolism modulates retention of inheritable sperm histones and early embryonic gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Cohesin complex members have recently been identified as putative tumor suppressors in hematologic and epithelial malignancies. The cohesin complex guides chromosome segregation, however cohesin-mutant leukemias do not show genomic instability. We hypothesized reduced cohesin function alters chromatin structure and disrupts cis-regulatory architecture of hematopoietic progenitors. We investigated the consequences of Smc3 deletion in normal and malignant hematopoiesis. Bi-allelic Smc3 loss induced bone marrow aplasia with premature sister chromatid separation, and revealed an absolute requirement for cohesin in hematopoietic stem cell function. In contrast, Smc3 haploinsufficiency increased self-renewal in vitro and in vivo including competitive transplantation. Smc3 haploinsufficiency reduced coordinated transcriptional output, including reduced expression of transcription factors and other genes associated with lineage commitment. Smc3 haploinsufficiency cooperated with Flt3-ITD to induce acute leukemia in vivo, with potentiated Stat5 signaling and altered nucleolar topology. These data establish a dose-dependency for cohesin in regulating chromatin structure and hematopoietic stem cell function. Overall design: mRNA-seq in murine c-kit+ cells for the following genotypes: Smc3 fl/+, Smc3 del/+, Flt3-ITD, Smc3 fl/del Flt3-ITD
Publication Title
Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina HiSeq 2000
Description
Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH. Functional studies have shown these mutations contribute to transformation, although how these mutations impact the response to epigenetic therapies is not fully delineated. Here we show AMLs with TET2/IDH2 mutations combined with FLT3ITD mutations are specifically sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. 5-Azacytidine/AG-221 therapies induced a reduction in leukemic blasts and in stem/progenitor expansion, with attenuation of aberrant DNA hypermethylation. These therapeutic benefits were achieved through restoration of differentiation, such that normalized hematopoiesis was derived from mutant cells. Consistent with these data, at the time of clinical response to 5-Azacytidine or AG-221, most patients had mutant-derived hematopoiesis. By contrast, combined AG-221/5-Azacytidine plus FLT3 inhibition reduced disease burden and reversed epigenetic dysfunction. Our studies suggest combined targeting of signaling and epigenetic pathways can increase therapeutic response in AML. Overall design: We profiled genome-wide transcription patterns of the hematopoietic stem cells (LSK) population in Wild-type, Idh2 R140Q Flt3-ITD, and Tet2-/-;Flt3-IDT mice. Idh2 R140Q Flt3-ITD mice with AML were treated with either vehicle or AG-221 (the first small molecule in vivo inhibitor of IDH2 to enter clinical trials). Tet2-/-;Flt3-IDT mice with AML were treated with vehicle or 5-Azacytidine (Decitabine, hypomethylating agent).
Publication Title
Combination Targeted Therapy to Disrupt Aberrant Oncogenic Signaling and Reverse Epigenetic Dysfunction in <i>IDH2</i>- and <i>TET2</i>-Mutant Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Using RNA-seq we identified the gene expression changes in GC B cells from LSD1 wild-type or LSD1-deficient mice immunized with T cell dependent antigens (Sheep Red Blood cells) Overall design: RNA seq of sorted GC B cell populations from 3 littermate mice per genotype (3 wild-type, 3 knockout)
Publication Title
Histone demethylase LSD1 is required for germinal center formation and BCL6-driven lymphomagenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PDE4 inhibitors, which activate cAMP signaling by reducing cAMP catabolism, are known to induce apoptosis in B lineage chronic lymphocytic leukemia (CLL) cells but not normal human T cells. The explanation for such differential sensitivity remains unknown. Here, we report studies contrasting the response to PDE4 inhibitor treatment in CLL cells and normal human T and B cells.
Publication Title
Chronic lymphocytic leukemia and B and T cells differ in their response to cyclic nucleotide phosphodiesterase inhibitors.
Sample Metadata Fields
No sample metadata fields
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