To find BMAL1-regulated genes in mice pituitary gland we performed a differential microarray from wild-type vs Bmal1-/- knock-out mice
Chromatin remodeling as a mechanism for circadian prolactin transcription: rhythmic NONO and SFPQ recruitment to HLTF.
Sex, Specimen part
View SamplesPurpose: Nephron progenitor cells generate nephrons, the basic units of kidney. We developed methods to culture mouse and human NPCs in their self-renewal state in vitro with full nephrogenic potentials. The RNA-seq here is used to compare the global gene expression of long-term cultured mouse NPCs and their cognate freshly isolated primary NPCs Methods: mRNA profiles were generated by deep sequencing in duplicate from E11.5, E12.5, E13.5, E16.5 and P1 primary NPCs, and from long-term cultured NPCs derived from E11.5, E13.5, E16.5 and P1 (Passage 20 and Passage 80 for each cell line). To generate rpkm values from raw data, single-end 50bp reads were mapped to the UCSC mouse transcriptome (mm9) by STAR9, allowing for up to 10 mismatches (which is the default by STAR). Only the reads aligned uniquely to one genomic location were retained for subsequent analysis. And expression levels of all genes were estimated by Cufflink10 using only the reads with exact matches. Results: The gene expression levels of the "NPC-signature genes" were firstly transformed as logarithm scales. And then the program “prcomp”, a built-in program for principal component analysis in R packages, was employed with default parameters. We evaluated the variance percentage of each principal component, and found the top 3 components accounted for 84.1% of the total variance, where PC1 accounted for 46.42%, PC2 23.87% and PC3 13.81%. Those three PCs are therefore selected as candidate principal components in the further analysis. Another program “scatterplot3d” in the R packages was used to plot the 3D view of PCA, and “ggplot2” was used in 2D view of PCA. The PCA results indicate that cultured NPCs cluster together in PCA analysis while primary NPCs segregate into early (E11.5 to E13.5) and later (E16.5, P1) NPC groups. Interestingly, cultured NPCs are close to early NPCs in both PC1 and PC2 axes, suggesting that cultured NPCs are maintained in state close to early NPCs. The close cluster of P20 and P80 NPCs show the robustness of our culture condition in maintaining stable self-renewal state of NPCs. Conclusions: Our study represents the first analysis comparing the long-term cultured NPC lines we geneated with primary NPCs, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions. Overall design: mRNA profiles were generated by deep sequencing in duplicate from E11.5, E12.5, E13.5, E16.5 and P1 primary NPCs, and from long-term cultured NPCs derived from E11.5, E13.5, E16.5 and P1 (Passage 20 and Passage 80 for each cell line)
3D Culture Supports Long-Term Expansion of Mouse and Human Nephrogenic Progenitors.
Specimen part, Cell line, Subject
View SamplesA chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blind, placebo controlled study in current heavy smokers to compare modulating effects of intermittent versus continuous low dose ASA on gene signatures of smoking and lung cancer from nasal brushings. Fifty-four participants were randomized to intermittent ASA (ASA 81 mg daily for one week alternating with placebo daily for one week) or continuous ASA (81 mg daily) for 12 weeks. The primary endpoint was modulation of a smoking gene signature in nasal brushings. Other [JB1] endpoints included modulation of nasal and bronchial gene signatures for smoking, lung cancer and chronic obstructive pulmonary disease (COPD) and changes in cyclooxygenase (COX)- and 5-lipoxygenase (LOX)-mediated arachidonic acid (ARA) metabolism.
Effect of Intermittent Versus Continuous Low-Dose Aspirin on Nasal Epithelium Gene Expression in Current Smokers: A Randomized, Double-Blinded Trial.
Sex, Age, Subject, Time
View SamplesThe anterior pituitary-specific transcription factor POU1F1 (also called PIT-1) was initially identified and cloned as a transactivator of PRL, GH and TSH subunit genes. Different studies indicated that POU1F1 could also have other functions in these cells. The identification of new targets of this factor could be useful to obtain a better understanding of these functions.
Research resource: A genome-wide study identifies potential new target genes for POU1F1.
Specimen part
View SamplesThis dataset describe the transcriptomic profiling of adult brain, gonades (testis and ovaries) of adult zebrafish exposed to 20µg/L of depleted uranium for 10 days. The progeny of the exposed fishes were also analysed at two-cells stage and 96 hours post fertilization Overall design: Biological samples (adult dissected tissues and whole embryos and larvae) were tested by RNASeq in duplicates
Whole transcriptome data of zebrafish exposed to chronic dose of depleted uranium.
No sample metadata fields
View SamplesNonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease and a leading cause of liver transplantation in the United Sates. Hedgehog (Hh) signaling has been implicated in liver lipid metabolism and the early stages of NAFLD; however, its precise role remains unclear. We examined the prevalence of NAFLD in patients with overt or microform holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Hh signaling. To test the hypothesis that Hh signaling attenuation predisposes to liver steatosis, we subjected Gli2 heterozygous null (Gli2+/-) mice to two unique dietary models of fatty liver. Compared to the general population, the prevalence of NAFLD was significantly higher in the HPE cohort independent of obesity, especially among younger individuals. Gli2 heterozygosity caused increased weight gain and liver steatosis on a high fat diet, and increased liver steatosis in the absence of weight gain on a methionine and choline deficient diet. Increased liver steatosis in Gli2+/- mice was associated with decreased expression of pro-fibrotic and pro-inflammatory genes and increased expression of PPAR, a potent anti-fibrogenic and anti-inflammatory regulator. In addition, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2+/- mice. Our results indicate that germline mutations affecting Hh signaling predispose to NAFLD with reduced or absent fibrosis, and might increase the risk of hepatocellular carcinoma.
Human germline hedgehog pathway mutations predispose to fatty liver.
Specimen part
View SamplesThe acute response four hours after a fat load of extra virgin olive oil was investigated using DNA microarrays. Hepatic gene expression was analysed in Wistar Rats.
Postprandial transcriptome associated with virgin olive oil intake in rat liver.
Sex, Age, Specimen part
View SamplesTwo olive oils only differing in the presence of maslinic acid were prepared. Using DNA microarrays, hepatic gene expression was analysed in apoE-deficient mice with a C57BL/6J genetic background
Apolipoprotein E determines the hepatic transcriptional profile of dietary maslinic acid in mice.
No sample metadata fields
View SamplesThe proper balance of excitatory and inhibitory neurons is crucial to normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors, Ascl1 and Ptf1a, are essential for generating the correct number and sub-type of neurons in multiple regions of the nervous system. Â In the dorsal spinal cord, Ascl1 and Ptf1a have contrasting functions in specifying inhibitory versus excitatory neurons. To understand how Ascl1 and Ptf1a function in these processes, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a regulate the specification of excitatory and inhibitory neurons in the dorsal spinal cord through direct regulation of distinct homeodomain transcription factors known for their function in neuronal sub-type specification. Besides their roles in regulating these homeodomain factors, Ascl1 and Ptf1a each function differently during neuronal development with Ascl1 directly regulating genes with roles in several steps of the neurogenic program including, Notch signaling, neuronal differentiation, axon guidance, and synapse formation. In contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover, Ptf1a represses the excitatory neuronal fate by directly repressing several targets of Ascl1. Examination of the Ascl1 and Ptf1a bound sequences shows they are enriched for a common E-Box with a GC core and with additional motifs used by Sox, Rfx, Pou, and Homeodomain factors. Ptf1a bound sequences are uniquely enriched in an E-Box with a GA/TC core and in the binding motif for its co-factor Rbpj, providing two keys to specificity of Ptf1a binding. The direct transcriptional targets identified for Ascl1 and Ptf1a provide a molecular understanding for how they function in neuronal development, particularly as key regulators of homeodomain transcription factors required for neuronal sub-type specification. Overall design: Examination of gene expression in Ascl1 and Ptf1a lineage cells in the developing neural tube.
A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord.
No sample metadata fields
View SamplesThis study supports an active role for PLZF and RAR-PLZF in leukemogenesis, identifies upregulation of CRABPI as a novel mechanism contributing to retinoid resistance and reveals the ability of the reciprocal fusion gene products to mediate distinct
RARalpha-PLZF overcomes PLZF-mediated repression of CRABPI, contributing to retinoid resistance in t(11;17) acute promyelocytic leukemia.
No sample metadata fields
View Samples