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SRP069190
Danio rerio
24 Downloadable Samples
IlluminaHiSeq2500
Description
Lymphocytes represent basic components of vertebrate adaptive immune systems, suggesting the utility of non-mammalian models to define the molecular basis of their development and differentiation. Our forward genetic screens in zebrafish for recessive mutations affecting early T cell development revealed several major genetic pathways. The identification of lineage-specific transcription factors and specific components of cytokine signaling and DNA replication/repair pathways known from studies of immuno-compromised mammals provided an evolutionary cross-validation of the screen design. Unexpectedly, however, certain pre-mRNA processing factor genes, including tnpo3, encoding a regulator of alternative splicing, were also found to play a specific role in early T cell development. In both zebrafish and mouse, TNPO3 deficiency impairs intrathymic T cell differentiation, illustrating evolutionarily conserved and cell type-specific functions of certain pre-mRNA processing factor. Overall design: Taking advantage of the apparent evolutionary conservation of lymphocyte-based immunity, we conducted genetic screens in zebrafish aimed at identifying novel regulators of T lymphocyte development. Apart from mutations in genes encoding lymphoid lineage-specific transcription factors, and components of cytokine signaling and DNA replication/repair pathways, mutations in genes encoding pre-mRNA processing factors were also found. To examine the molecular consequences, transcriptome analyses were conducted for three mutants, snapc3, lsm8, tnpo3.
Publication Title
Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 8 Downloadable Samples
Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
In the present study, we sought to understand the impact of obesity/metabolic disease (high-fat induced) on spinal cord injury (SCI) by examining transcriptome. Adult, male Long Evans rats received either thoracic level contusion of the spinal cord or sham laminectomy and then were allowed to recover on normal rat chow for 4 weeks and further on HFD for an additional 8 weeks. Spinal cord tissues harvested from the rats were processed for Affymetrix microarray and further transcriptomic analysis.
Publication Title
Chronic spinal cord changes in a high-fat diet-fed male rat model of thoracic spinal contusion.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 3 Downloadable Samples
- IlluminaGenomeAnalyzer
Description
Through deep sequencing and functional screening in zebrafish, we find that miR-221 is essential for angiogenesis. miR-221 knockdown phenocopied defects associated with loss of the tip cell-expressed Flt4 receptor. Furthermore, miR-221 was required for tip cell proliferation and migration, as well as tip cell potential in mosaic blood vessels. miR-221 knockdown also prevented “hyper-angiogenesis” defects associated with Notch deficiency and miR-221 expression was inhibited by Notch signaling. Finally, miR-221 promoted tip cell behavior through repression of two targets: cyclin-dependent kinase inhibitor 1b (cdkn1b) and phosphoinositide-3-kinase regulatory subunit 1 (pik3r1). These results identify miR-221 as an important regulatory node through which tip cell migration and proliferation are controlled during angiogenesis. Overall design: Identification of endothelial-expressed microRNA from FACS-isolated zebrafish endothelial cells.
Publication Title
miR-221 is required for endothelial tip cell behaviors during vascular development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The etiology of ovarian cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mouse model termed ERalpha d/d in which a conditional deletion of estrogen receptor alpha (ERalpha) gene occurred in the anterior pituitary, but ERalpha expression remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E) at the level of the pituitary led to elevated production of luteinizing hormone (LH) by this tissue. Hyperstimulation of ovarian cells by LH resulted in increased steroidogenesis, leading to high circulating levels of progesterone, testosterone and E. The ERalpha d/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age, and by 12 months, most mice carrying these tumors died. Besides proliferating epithelial cells, these tumors also contained an expanded population of stromal cells, which express P450 aromatase suggesting that these cells acquired the ability to synthesize E. In ERalpha d/d mice, in response to the E produced by the stromal cells, the ERalpha signaling is accentuated in the ovarian epithelial cells, triggering increased ERalpha-dependent gene expression, abnormal cell proliferation, and tumorigenesis. The ERalpha d/d animal model of ovarian epithelial tumorigenesis will serve as a powerful tool for exploring the involvement of E-dependent signaling pathways in the etiology of ovarian cancer.
Publication Title
Dysregulated estrogen receptor signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Placenta development involves complex molecular and cellular interactions between the maternal endometrium and the developing embryo, however, it is not clear what are the precise mechanisms regulating this maternal-fetal crosstalk. Using genetic and cell biological approaches, we have demonstrated that Ras-related C3 botulinum toxin substrate 1 (Rac1), a maternal factor expressed in decidual cells and is markedly elevated in mouse decidua on days 7 and 8 of gestation, regulates the secretory pathways that mediate stromal-endothelial and stromal-trophoblast crosstalk within a narrow temporal window during placenta development.
Publication Title
Rac1 Regulates Endometrial Secretory Function to Control Placental Development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
To gain insights into the genes whose expression levels are altered during stromal cell differentiation (decidualization), gene microarray profiling was performed following the experimentally induced decidualization protocol.
Publication Title
Rac1 Regulates Endometrial Secretory Function to Control Placental Development.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Our study revealed that hypoxia inducible factor 2 alpha, Hif2 alpha, is a downstream target of estrogen signaling in mouse uterine stroma at the time of implantation. Further, conditional deletion of Hif2 alpha in mouse uterus leads to infertility due to impaired epithelial remodeling at the time of implantation.
Publication Title
A hypoxia-induced Rab pathway regulates embryo implantation by controlled trafficking of secretory granules.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
LbetaT2 cells exposed to different number and concentration of GnRH pulses over 4 hours during in vitro perfusion culture
Publication Title
Pulse sensitivity of the luteinizing hormone beta promoter is determined by a negative feedback loop Involving early growth response-1 and Ngfi-A binding protein 1 and 2.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
This study was designed to compare the global gene expression change induced by the circulating, prodomain bound forms of BMP9 and BMP10 (pro-BMP9 and pro-BMP10) in human pulmonary arterial endothelial cells (PAECs). This is different from many previous studies which used the growth factor domain of BMP9 and/or BMP10.
Publication Title
Molecular basis of ALK1-mediated signalling by BMP9/BMP10 and their prodomain-bound forms.
Sample Metadata Fields
Sex, Age
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
In the present study, we sought to understand the impact of bariatric surgery [using vertical sleeve gastrectomy (VSG)] on transcriptome changes in the placenta . Female Adult, Long Evans were fed high fat diet (HFD, #D03082706, Research Diets) for 4 weeks, divided into sham-VSG or VSG groups, and following surgeries one group of sham-VSG and VSG were switched to normal diet (lean), while one sham-VSG group (obese) continued HFD. At gestdational day 18, placenta tissues harvested from pregnant female rats were processed for Affymetrix microarray and transcriptomic analysis performed.
Publication Title
Rodent vertical sleeve gastrectomy alters maternal immune health and fetoplacental development.
Sample Metadata Fields
Age
View Samples