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SRP030657
Danio rerio
2 Downloadable Samples
IlluminaHiSeq2000
Description
To comprehensively reflect the impact of RPL11 deficiency on the transcriptome of zebrafish embryos, we collected 40–50 RPL11-deficient and MO control zebrafish embryos at 48 hpf from separate experiments and constructed two mRNA-seq sequencing libraries in parallel. High-throughput sequencing was performed on the Hi-Seq2000 sequencing platform in parallel. The number of sequenced gene transcript reads was 35–40 million. We found that hemoglobin biosynthetic and hematological defects in RPL11-deficient zebrafish were related to dysregulation of iron metabolism-related genes, including tfa, tfr1b, alas2 and slc25a37, which are involved in heme and hemoglobin biosynthesis. In addition, we found reduced expression of the hematopoietic stem cells (HSC) marker c-myb and HSC transcription factor tal1 and hoxb4a in RPL11-deficient zebrafish embryos, indicating that the hematopoietic defects may be related to impaired HSC differentiation and proliferation. However, RPL11 deficiency did not affect the development of other blood cell lineages such as granulocytes and myelocytes. Overall design: Compare 2 different transcriptomes of RPL11-deficient and MO control zebrafish embryos
Publication Title
Transcriptome analysis of Rpl11-deficient zebrafish model of Diamond-Blackfan Anemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
In this study, we generated a zebrafish model of DBA with RPL5 morphants and implemented high-throughput RNA-seq and miRNA-seq to identify key genes, lncRNAs, and miRNAs during zebrafish development and hematopoiesis. We found that RPL5 is required for both primitive and definitive hematopoiesis processes that are partially mediated by the P53 pathway. Several genes such as cirh1a, noc2l, tars, and nol6 and miRNAs such as dre-miR-10a*, dre-miR-722, dre-miR-737, and dre-miR-142a-3p were significantly deregulated, and these changes may play a crucial role in hematopoiesis, ribosome biogenesis and development process. We also characterized the lncRNome in zebrafish with RPL5 deficiency. By constructing a comprehensive regulatory network, we identified central node genes in the network connected to the P53 pathway, almost all of which were targeted by the significantly deregulated miRNAs listed above. Our results therefore establish a regulatory network for critical genes and miRNAs involved in the RPL5-deficient zebrafish model and provide a comprehensive basis for the molecular pathogenesis of RPL5-mediated DBA and other ribosomopathies. Overall design: Determine the differences of transcriptome between RPL5-deficient and MO control zebrafish embryos for understanding the complex molecular pathogenesis of mutant RPL5-mediated human diseases
Publication Title
Transcriptome analysis reveals a ribosome constituents disorder involved in the RPL5 downregulated zebrafish model of Diamond-Blackfan anemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Sin3a, a known master scaffold, provides unique contact surfaces for interaction with particular accessory proteins to repress the transcription of specific genes. Surprisingly, our results also suggest that Sin3a has a role in transcriptional activation.
Publication Title
Sin3a-Tet1 interaction activates gene transcription and is required for embryonic stem cell pluripotency.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 19 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Anti-inflammatory properties of alpha- and gamma-tocopherol.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Keratinocytes are the major constituent of epithelial cells at mucosal surfaces and skin, which cover organs, internal cavities and the body. Traditionally, keratinocytes have been considered as an inert component of the multilayered epithelium to protect the subepithelial compartments from the pathogenic microorganisms, toxic stimuli and physical trauma. However, accumulated researches of the airway, gastrointestinal tract and skin have demonstrated that keratinocytes function in the development of the immune system, promotion of pathologic inflammation and even impose diverse decisions on immune cells.
Publication Title
Genome-wide analysis reveals the active roles of keratinocytes in oral mucosal adaptive immune response.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 31 Downloadable Samples
Description
Rorb is essential for rod photoreceptor development in the mouse retina. Using Affymetrix mouse GeneChips, we have generated expression profiles of the +/+, Rorb-/- , +/+;CrxpNrl and Rorb-/-;CrxpNrl retina at P14 and P28.
Publication Title
Retinoid-related orphan nuclear receptor RORbeta is an early-acting factor in rod photoreceptor development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
RAS oncogenic mutations are common in human cancers, but RAS proteins have been difficult to target. We sought to identify pharmacological agents to block the RAS oncogenic signaling by a distinct mechanism. Since the biological activity of RAS proteins rely upon lipid modifications and RAS regulates lipid metabolisms in cancer cells, we screened a bioactive lipid library using a RAS specific cell viability assay. We report the discovery of a new class of inhibitors for RAS transformation. Compounds in the class represented by endocannabinoid N-arachidonoyl dopamine (NADA) can induce cell oncosis, independent of its ability to engage cannabinoid receptors. Further analyses show that NADA is more active in inhibiting the NRAS transformation and signaling than that of KRAS4B. Mechanistically, NADA blocks the plasma membrane translocation of NRAS, but not that of KRAS4B. In addition, NADA inhibits the plasma membrane translocation and neoplastic transformation of oncogenic KRAS4A. Interestingly, NADA also redistributes the cytoplasmic NRAS to the Golgi apparatus in a palmitoylation-dependent manner. The results indicate that NADA inhibits NRAS and KRAS4A plasma membrane translocation by targeting a novel molecular process. The new findings would help to develop novel targeted therapies for a broad range of human cancers.
Publication Title
N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 20 Downloadable Samples
Description
Psoriasis is a complex inflammatory disease resulting from the activation of T helper (Th) 1 and Th17 cells. Recent evidence suggests that abnormal activation of Toll-like receptors (TLRs) 7, 8 and 9 contributes to the initiation and maintenance of psoriasis. We have evaluated the effects of TLR antagonists on the gene expression profile in an IL-23-induced skin inflammation model in mice. Psoriasis-like skin lesions were induced in C57BL/6 mice by intradermal injection of IL-23 in the dorsum. Two TLR antagonists were compared: IMO-3100, an antagonist of TLRs 7 and 9, and IMO-8400, an antagonist of TLRs 7, 8 and 9, both of which previously have been shown to reduce epidermal hyperplasia in this model. Skin gene expression profiles of IL-23-induced inflammation were compared with or without TLR antagonist treatment. IL-23 injection resulted in alteration of 5100 gene probes (fold change 2, FDR < 0.05) including IL-17 pathways that are up-regulated in psoriasis vulgaris. Targeting TLRs 7, 8 and 9 with IMO-8400 resulted in modulation of more than 2300 mRNAs while targeting TLRs 7 and 9 with IMO-3100 resulted in modulation of more than 1900 mRNAs. Both agents strongly decreased IL-17A expression (>12-fold reduction), normalized IL-17 induced genes such as beta-defensin and CXCL1, and normalized aberrant expression of keratin 16 (indicating epidermal hyperplasia). These results suggest that IL-23-driven inflammation in mouse skin may be dependent on signaling mediated by TLRs 7, 8, and 9 and that these receptors represent novel therapeutic targets in psoriasis vulgaris and other diseases with similar pathophysiology.
Publication Title
Suppression of molecular inflammatory pathways by Toll-like receptor 7, 8, and 9 antagonists in a model of IL-23-induced skin inflammation.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
Description
We performed miRNA and mRNA profiling in BASC cells and c-Myc depleted BASC cells. We built potential miRNA-mRNA interaction networks specific to c-Myc regulation in BASCs
Publication Title
c-Myc regulates self-renewal in bronchoalveolar stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Analysis of heart ventricles from Hopx, Hdac2, and both Hopx-Hdac2 deficient embryos at embryonic day E16.5. Results provide insight into the role of Hopx and Hdac2 in cardiac development.
Publication Title
Hopx and Hdac2 interact to modulate Gata4 acetylation and embryonic cardiac myocyte proliferation.
Sample Metadata Fields
Specimen part
View Samples