The study of the role of Drosophila Ada2b SAGA histone acetyltransferase component at early pupal stage (P4)
Genes of the ecdysone biosynthesis pathway are regulated by the dATAC histone acetyltransferase complex in Drosophila.
Sex, Age, Time
View SamplesT4 and T5 neurons are components of the neuronal circuit for motion vision in flies. To identify genes involved in neuronal computation of T4 and T5 neurons, we perfomed transcriptome analysis. Nuclei of T4 and T5 neurons were immunoprecipitated, total RNA was harvested and used for mRNA-seq with Illumina technology. In two biological replicates, we mapped 154 and 119 million reads to D. melanogaster genome. mRNA-seq provided information about expression levels of 17,468 annotated transcripts in the T4 and T5 neurons. Overall design: Cell type – specific transcriptome analysis of the RNA isolated from immunoprecipitated nuclei, performed in two biological replicates
RNA-Seq Transcriptome Analysis of Direction-Selective T4/T5 Neurons in Drosophila.
Subject
View SamplesRNA seq analyses were performed in granulosa cells (GCs) collected from gonadotropin treated ESR2 mutant rats. Data obtained from a null mutant with Esr2 exon 3 deletion (?3) and another DNA binding domain (DBD) mutant with exon 4 deletion (?4) were compared to that of wildtype (WT) rats. The raw data were analyzed using CLC genomics workbench. High quality RNA-sequencing reads were aligned to the Rattus norvegicus genome. Differentially expressed genes in ?3 or ?4 Esr2-mutant GCs were identified based on the following criteria: FDR p-Value =0.05 and an absolute fold change of 2. Fewer differentially expressed genes were identified in ?3 compared to the ?4 mutant group. As both of the mutant groups demonstrated a common phenotype of ovulation failure, differentially expressed genes common to both in ?3 and ?4 mutant rats were emphasized and further analyzed in the companion article “ESR2 regulates granulosa cell genes essential for follicle maturation and ovulation” (Khristi et al., 2018).
ESR2 regulates granulosa cell genes essential for follicle maturation and ovulation.
No sample metadata fields
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Integrated transcriptomic and epigenomic analysis of primary human lung epithelial cell differentiation.
Sex, Specimen part, Time
View SamplesThe Iroquois homeodomain transcription factor gene IRX3 is highly expressed in the developing nervous system, limb buds and heart. In adults, expression levels specify risk of obesity. We now report a significant functional role for IRX3 in human acute leukemia. While transcript levels are very low in normal human bone marrow cell populations, high level IRX3 expression is observed in ~30% of patients with acute myeloid leukemia (AML), ~50% of patients with T-acute lymphoblastic leukemia and ~20% of patients with B-acute lymphoblastic leukemia, typically in association with high levels of HOXA9. Expression of IRX3 alone was sufficient to immortalise murine bone marrow stem and progenitor cells, and induce T- and B-lineage leukemias in vivo with incomplete penetrance. IRX3 knockdown induced terminal differentiation of AML cells. Combined IRX3 and Hoxa9 expression in murine bone marrow stem and progenitor cells substantially enhanced the morphologic and phenotypic differentiation block of the resulting AMLs by comparison with Hoxa9-only leukemias, through suppression of a myelomonocytic program. Likewise, in cases of primary human AML, high IRX3 expression is associated with reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression of IRX3 modulates the cellular consequences of HOX gene expression to enhance differentiation block in human AML. Overall design: Murine acute myeloid leukemias - 3 samples from separate mice with AML initiated by HOXA9 and 3 samples from separate mice with AML initiated by HOXA9 and IRX3 coexpression
Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia.
Specimen part, Cell line, Subject
View SamplesAnalysis of gene expression during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells. Timepoints taken at Day 0 (AT2 cell), Days 2, 4, and 6 in culture (differentiating) and Day 8 in culture (AT1-like cells).
Integrated transcriptomic and epigenomic analysis of primary human lung epithelial cell differentiation.
Sex, Specimen part, Time
View SamplesThe activation of endothelium by tumor cells is one of the main steps by tumor metastasis. The role of the blood components (platelets and leukocytes) in this process remain unclear.
Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes.
Specimen part
View SamplesDiseases involving the distal lung alveolar epithelium include chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and lung adenocarcinoma. Accurate labeling of specific cell types is critical for determining the contribution of each to pathogenesis of these diseases. The distal lung alveolar epithelium is comprised of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. While cell type-specific markers, most prominently surfactant protein C (SFTPC), have allowed detailed studies of AT2 cell differentiation and their roles in disease, studies of AT1 cells have been hampered by lack of genes with expression unique to AT1 cells. To address this, we performed genome-wide expression profiling of multiple rat organs alongside purified rat AT2, AT1 and in vitro differentiated AT1-like cells, resulting in identification of 54 candidate AT1 cell markers. Cross-referencing with genes upregulated in human in vitro differentiated AT1-like cells narrowed the potential list to 18 candidate genes. Testing the top four candidate genes at RNA and protein levels revealed GRAM domain 2 (GRAMD2), a protein of unknown function, as unique to AT1 cells, while SCNN1G within lung is restricted to AT1 cells. RNAseq confirmed that GRAMD2 is transcriptionally silent in human AT2 cells. Immunofluorescence of mouse alveoli verified that GRAMD2 expression is restricted to the plasma membrane of AT1 cells. These new AT1 cell-specific genes, with GRAMD2 as a leading candidate, will enhance AT1 cell isolation, investigation of alveolar epithelial cell differentiation potential, and contribution of AT1 cells to distal lung diseases. Overall design: RNAseq of purified primary human alveolar epithelial type 2 (AT2) and in vitro differentiated type 1 (AT1-like) cells.
Cross-Species Transcriptome Profiling Identifies New Alveolar Epithelial Type I Cell-Specific Genes.
No sample metadata fields
View SamplesIt It is known that functional maturation of the small intestine occurring during the weaning period is facilitated by glucocorticoids (such as hydrocortisone, HC) including the increased expression of digestive hydrolases. However, the molecular mechanism(s) are not well understood, particularly in human gut. Here we report a microarray analysis of HC- induced changes in gene expression in H4 (a human fetal small intestinal epithelial cell line well-characterized in numerous previous studies). This study identified a large number of HC-affected genes, some involved in metabolism, cell cycle regulation, cell polarity, tight junction formation, and interactions with extracellular matrices. These effects could play an important role in HC-mediated enterocyte maturation in vivo and in vitro.
Hydrocortisone induces changes in gene expression and differentiation in immature human enterocytes.
Cell line, Treatment
View SamplesSmoking-associated DNA hypomethylation has been observed in blood cells and linked to lung cancer risk. However, its cause and mechanistic relationship to lung cancer remain unclear. We studied the association between tobacco smoking and epigenome-wide methylation in non-tumor lung (NTL) tissue from 237 lung cancer cases in the Environment And Genetics in Lung cancer Etiology study, using the Infinium HumanMethylation450 BeadChip. We identified seven smoking-associated hypomethylated CpGs (P?<?1.0?×?10-7), which were replicated in NTL data from The Cancer Genome Atlas. Five of these loci were previously reported as hypomethylated in smokers'' blood, suggesting that blood-based biomarkers can reflect changes in the target tissue for these loci. Four CpGs border sequences carrying aryl hydrocarbon receptor binding sites and enhancer-specific histone modifications in primary alveolar epithelium and A549 lung adenocarcinoma cells. A549 cell exposure to cigarette smoke condensate increased these enhancer marks significantly and stimulated expression of predicted target xenobiotic response-related genes AHRR (P?=?1.13?×?10-62) and CYP1B1 (P?<?2.49?×?10-61). Expression of both genes was linked to smoking-related transversion mutations in lung tumors. Thus, smoking-associated hypomethylation may be a consequence of enhancer activation, revealing environmentally-induced regulatory elements implicated in lung carcinogenesis. Overall design: RNAseq of DMSO or cigarette smoke condensate (CSC)-treated A549 human lung adenocarcinoma cells. Cells were treated for either 48 hours or 2 weeks, as indicated.
Epigenome-wide analysis of DNA methylation in lung tissue shows concordance with blood studies and identifies tobacco smoke-inducible enhancers.
No sample metadata fields
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