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GSE30318
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used gene expression microarrays to identify genes whose expression was influenced differently by TNFa in Fancc-deficient mice compared to wild type (WT) mice. To identify genes whose expression was directly or indirectly influenced by Fancc, we looked in particular for genes either suppressed or induced by TNF in WT cells that were not affected by TNF in Fancc-deficient cells.
Publication Title
FANCL ubiquitinates β-catenin and enhances its nuclear function.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
the molecular mechanisms for the biphasic effect of alcohol are not fully understood. The goal of the study is to identify genes that are differentially expressed following alcohol exposure of 50mM and 100mM ethanol for 24 hours.
Publication Title
Ethanol upregulates glucocorticoid-induced leucine zipper expression and modulates cellular inflammatory responses in lung epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 20 Downloadable Samples
Illumina HiSeq 2000
Description
We used Fancd2-/- mice to understand its mechanism of action. Transcriptome analysis of cKit+ Sca1+ Lin- (KSL) cells discovered that only four genes changed their expression levels significantly after chronic OXM administration in both Fancd2-/- and wild-type mice: mKi67 and Cenpf were up-regualted by 1.4 fold; Spp1 and Oasl2 were significantly down-regulated by 10.5 and 1.5 fold, respectively. Both mKi67 and Cenpf genes are cell cycle-regulated genes and proliferation markers. Their up-regulation was consistent with our observation in flow cytometry analysis that oxymetholone stimulated the proliferation of hematopoietic stem and progenitor cells. RNAseq analysis showed no effects on mTert mRNA expression with chronic androgen therapy, but instead suggested down-regulation of Spp1 and Oasl2 as an important mechanism for the drug’s action. Our RNAseq analysis also revealed that Fancd2-/- KSL cells showed clear changes in mRNA expression profiles compared to wild-type controls: 430 genes were down-regulated by more than 1.5 fold, whereas 159 genes were up-regulated. Gene ontology analysis revealed key pathways to be significantly altered in Fancd2-/- KSL cells. Besides the abnormal cell cycle status expected from our earlier flow cytometry analysis, surprisingly we noticed that a group of genes involved in immune responses and inflammation, comprising Cfp (Properdin), Socs2, Ccr1, Ccr2, Ccr5, Chga (Chromogranin A), Ifi30 (Interferon Gamma-Inducible Protein 30), Lgmn, Txn, and Sell (selectin L), were up-regulated in Fancd2-/- KSL cells. We therefore hypothesize that some genes up-regulated in FA HSPCs may be part of an innate immune response to DNA damage. In addition, whole bone marrow cells were also analyzed in parallel with KSL cells. As compared to whole bone marrow cells, the genes enriched in KSL cells in wild-type mice were listed in details in the corresponding publication. This information can be a good resource for the future gene expression analysis of HSPCs. Finally, we compared the gene expression profiles of early progenitors between OXM-treated and placebo-treated mice. There were no significant differences at all in gene expression between OXM-treated wild-type erythroid progenitors and their placebo-treated wild-type counterparts, with no genes displaying an expression change higher than 1.2 fold. Importantly, no up-regulation of EPO-inducible genes such as Socs1, Socs2, Socs3, and Cish was seen in wild-type mice treated with OXM. Furthermore, there was no differential expression of the well-known EPO target transferrin receptor or any other major players of the Epo-R signaling network such as Bcl2l1, Cdc25a, Btg3, Ccnd2, Lyl1, Pim3, and Tnfrsf13c. These results indicate that EPO might not play a role in the action of OXM in the erythroid lineage. Overall design: The goal of this study is to investigate gene expression changes in Fancd2 knockout mice in response to oxymetholone treatment. The study focuses on two bone marrow cell populations: cKit+ Sca1+ Lin- cells (representing hematopoietic stem and progenitor cells) and Ter119+/CD71high/FSChigh cells (representing proerythroblasts and basophilic erythroblasts). Both populations were sorted twice by FACS to ensure the purity. Cells of interest were collected in Trizol and RNA was isolated using RNAeasy mini prep kit. mRNAs were positively selected using oligo(dT)- Dynobeads and treated with DNase I. RNAseq libraries were then constructed using Illumina TruSeq RNA Sample Prep Kit and sequenced as 51 base-length reads on an Illumina HiSeq 2000 genome analyzer. For KSL libraries, each sample represented total mRNA isolated from pooled KSL cells of 5 individual mice; for basophilic erythroblast libraries, each library represented total mRNA isolated from basophilic erythroblasts of one individual mouse; for whole bone marrow libraries, each sample represented a combined library originally from 5 individual mice. All reads were mapped to the mouse reference genome (version mm9) using Bowtie short read aligner software (http://bowtie-bio.sf.net). Most of the data analysis was performed using EdgeR GLM algorithms. For the comparison of oxymetholone KSL libraries vs placebo KSL libraries, more stringent pair-wise comparisons were used to keep a consistent flow cytometric setting among each pair. The common gene list was the one shared by all three comparisons: COM17 vs HSC_101b, HSC_13 vs HSC_18, and HSC_23 vs QZ_35 for Fancd2-/- KSL cells; HSC_3 vs QZ_36, HSC_22 vs HSC_24, and COM15 vs COM16 for wild-type KSL cells. Data-mining and pathway analysis were carried out with the MetaCore integrated software suite (Thomson Reuters, New York, USA).
Publication Title
Oxymetholone therapy of fanconi anemia suppresses osteopontin transcription and induces hematopoietic stem cell cycling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Fanconi anemia (FA) is a rare inherited disease complicated by aplastic anemia. There is evidence that hematopoietic stem cells have lost self replicative capacity and undergo apoptosis when exposed to inhibitory cytokines including interferon gamma and tumor necrosis factor-alpha.
Publication Title
TLR8-dependent TNF-(alpha) overexpression in Fanconi anemia group C cells.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Our previous studies have shown that C/EBP plays a critical role in human endometrial stromal decidualization. In order to identify the molecular pathways regulated by C/EBP during decidualization, we performed gene expression profiling using RNA isolated from normal and C/EBP-deficient human endometrial stromal cells. The microarray results revealed that several key regulators of stromal differentiation, such as BMP2, Wnt4, IL-11R and STAT3, operate downstream of C/EBP during decidualization. Further studies revealed that STAT3 is a direct target of C/EBP and plays an important role in cytokine signal during the decidualization process. Gene expression profiling, using STAT3-deficient HESCs, showed an extensive overlap of pathways downstream of STAT3 and C/EBP during stromal cell differentiation.
Publication Title
Regulation of human endometrial stromal proliferation and differentiation by C/EBPβ involves cyclin E-cdk2 and STAT3.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ulipristal acetate (UPA), also referred to as VA/CDB-2914, is a new and promising emergency contraceptive. It is a selective progesterone receptor modulator (SPRM) that has been approved in Europe and the USA for emergency contraception.
Publication Title
Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Previous studies have shown that PR is a critical regulator of ovulation. The PR-null mice (PRKO) failed to ovulate due to a failure in the rupture of the preovulatory follicles.
Publication Title
Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
gene expression at 6h of differentiation of Human endometrial stromal cell expressing either or both of PRA and PRB
Publication Title
Roles of progesterone receptor A and B isoforms during human endometrial decidualization.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Estrogen and progesterone are important regulators of human endometrial differentiation. These steroid hormones act, at least in part, through their nucelar receptors. Role of estrogen receptor alpha (ESR1) during human endometrial differentiation is still unclear.
Publication Title
Roles of Estrogen Receptor-α and the Coactivator MED1 During Human Endometrial Decidualization.
Sample Metadata Fields
Specimen part
View Samples