Individuals with Trisomy 21 (T21) exhibit numerous hematological abnormalities, including reductions in numbers of circulating B and T lymphocytes. To elucidate molecular mechanisms underlying these phenotypes, we differentiated human isogenic disomic and trisomic pluripotent cells, and observed that trisomic cells showed defects in B cell, but not T, cell differentiation. Global gene expression of differentiated, trisomic B cells revealed reduced expression of genes encoding endothelin signaling components, namely the Endothelin Receptor B (Ednrb), and its ligand Endothelin1 (Edn1).. Depletion of Ednrb mRNA in cord blood CD34+ cells led to defective B cell differentiation, supporting an hypothesis that low expression of Ednrb in T21 contributes to intrinsic lymphoid defects. Further evidence for the role of the Ednrb pathway in B cell differentiation was obtained through CRISPR/Cas9 gene targeting in disomic and trisomic iPS cells. Knockout of Ednrb in both cell backgrounds reduced the capacity for B cell differentiation. Collectively, this work identifies downregulation of Ednrb as a causative factor for impaired B lymphocyte generation in trisomic cells, which may contribute to defects in immune function associated with T21. Furthermore, a novel role for endothelin signaling in regulation of B cell development has been identified.
Downregulation of Endothelin Receptor B Contributes to Defective B Cell Lymphopoiesis in Trisomy 21 Pluripotent Stem Cells.
Specimen part
View SamplesExpression data after flg22 treatment on leaf discs in Col-0, 35S:AFB1 and 35S:miR393
The microRNA miR393 re-directs secondary metabolite biosynthesis away from camalexin and towards glucosinolates.
Specimen part
View SamplesExpression data 24hrs after PstDC3000 inoculation in Col-0, 35S:AFB1 and 35S:miR393.
The microRNA miR393 re-directs secondary metabolite biosynthesis away from camalexin and towards glucosinolates.
Specimen part
View SamplesThe Arabidopsis cytochrome P450 KLUH (KLU)/CYP78A5 promotes organ growth in a non-cell autonomous manner. To identify genes regulated by KLU activity, homozygous klu-2 mutants carrying constructs for EtOH-inducible overexpression of wild-type KLU (35S::AlcR-AlcA::KLU) or of enzymatically inactive KLU protein (35S::AlcR-AlcA::KLUmut) were induced with EtOH and sampled at 90 min and 240 min after induction for gene expression changes.
Control of plant organ size by KLUH/CYP78A5-dependent intercellular signaling.
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View SamplesBecause niclosamide inhibits growth and progression of endometriotic lesions, we performed RNA-seq in order to identify genes whose expression is regulated by niclosamide in endometriotic lesions. Our results shown that niclosamide modulates several genes related to cell signaling, extracellular matrix, and inflammatory signaling. Overall design: A direct comparison of endometriotic like lesions developed in mice (n=3 per group) treated orally with either vehicle control or 200 mg/kg bw day of niclosamide for 3 weeks.
Niclosamide As a Potential Nonsteroidal Therapy for Endometriosis That Preserves Reproductive Function in an Experimental Mouse Model.
Sex, Specimen part, Cell line, Treatment, Subject
View SamplesThe floxed insulin receptor was specifically targetted for deletion in the mammary gland using a mouse strain bearing Cre recombinase under the BLG promoter.
The insulin receptor plays an important role in secretory differentiation in the mammary gland.
Specimen part
View SamplesRb null embryos exhibit defective fetal liver erythropoiesis. We used microarrays to compare Wt and Rb null fetal livers and to analyse gene expression differences which accompany and may underlie Rb null fetal liver degeneration, erythroid failure, and erythropoietic island dissolution.
Hypoxic stress underlies defects in erythroblast islands in the Rb-null mouse.
No sample metadata fields
View SamplesWe report the differential gene expression differences between control and Ovol2-deficent newborn keratinocytes Overall design: Two control and two Ovol2-deficent samples were isolated
An Ovol2-Zeb1 transcriptional circuit regulates epithelial directional migration and proliferation.
Specimen part, Subject
View SamplesThe absence of the Rb tumor suppressor gene changes levels/activities of transcription factors (e.g., E2F and p53) which alter gene expression patterns, related to cell cycle control and cellular response to DNA damage. Cisplatin is a genotoxic chemotherapeutic agent and wildtype or Rb null cells have different sensitivities to cisplatin-induced cytotoxicity.
Elevated poly-(ADP-ribose)-polymerase activity sensitizes retinoblastoma-deficient cells to DNA damage-induced necrosis.
No sample metadata fields
View SamplesDifferent strains of T. brucei induce different degrees of pathology in infected animals, and TREU927-infected mice display greater splenomegaly and anaemia than 247-infected mice. The analysis of differential host gene expression in infected spleens has allowed the identification of which pathways or processes are crucial in determining the progression of disease, for example IL10, LXR/RXR activation and alternative macrophage activation.
Role for parasite genetic diversity in differential host responses to Trypanosoma brucei infection.
Specimen part
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