Drosophila melanogaster adult males perform an elaborate courtship ritual to entice females to mate. fruitless (fru), a gene that is one of the key regulators of male courtship behavior, encodes multiple male-specific isoforms (FruM). These isoforms vary in their carboxy-terminal zinc finger domains, which are predicted to facilitate DNA binding. By over-expressing individual FruM isoforms in fru-expressing neurons in either males or females and assaying the global transcriptional response by RNA-sequencing, we show that three FruM isoforms have different regulatory activities that depend on the sex of the fly. We identified several sets of genes regulated downstream of FruM isoforms. Overall design: RNA seqeuncing was performed on mRNA derived from adult male or female heads, for a total of 39 samples. These samples included two wild type genotypes (Berlin and Canton-S), two transheterozygous mutants for fru P1 (Df(3R)P14/Df(3R)fru4-40 and fruw12/ Df(3R)ChaM5), and 3 overexpressing genotypes (fru P1-Gal4: UAS-FruMA, UAS-FruMB, UAS-FruMC). There were at least 3 replicates from biological samples for all sex by genotype combinations.
Sex Differences in Drosophila Somatic Gene Expression: Variation and Regulation by doublesex.
Sex, Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Nucleosome positioning changes during human embryonic stem cell differentiation.
Specimen part, Cell line
View SamplesThe Drosophila sex determination hierarchy consists of a splicing cascade with sex-specific transcription directing somatic sexual dimorphism. Our understanding of this pathway, and many others, is incomplete. Here we pioneer an approach to expand our knowledge of gene regulatory networks (GRNs) by leveraging natural genetic variation. This approach is generalizable to any natural population, including humans. Two studies from Drosophila female head tissue were used – the DSPR collection (alleles from 15 natural variants) and F1-hybrid collection (alleles from heterozygotes of 75 isogenic lines crossed to w1118) – in a structural equation model (SEM) analysis. We expanded the sex hierarchy GRN by adding novel links among genes in the pathway and by adding novel genes to the pathway. A link from fruitless (fru) to Sex-lethal (Sxl) was found in both populations, which is supported by the presence of fru binding sites in the Sxl locus. The splicing factors male-specific lethal 2 and Rm62 were correctly identified as downstream targets of Sxl. There were 754 additional candidate genes for an expanded sex hierarchy GRN. These candidates were enriched for genes with sex-biased splicing and many components of the spliceosome were placed in the GRN. As with other population-genetic analyses, the number of alleles limits the number of observable interactions. Network expansion was only clear in the F1-hybrid population, which has an average of twice as many alleles as the DSPR population. Independent studies of doublesex and transformer mutants support many novel connections, including evidence for a link between the sex hierarchy and metabolism, with the inclusion of Insulin-like receptor in the sex hierarchy GRN. Overall design: RNA sequencing was performed on mRNA derived from adult male or female heads, for a total of 9 samples. These samples included females that produce the male isoform of dsx [w/+;DsxD/dsxm+r15 (XX)], and two dsx mutants: females [w/+; dsxm+r15/dsxd+r3 (XX)] and males [w;dsxm+r15/dsxd+r3 (XY)]. Two wild type genotypes (Berlin and Canton-S) were sequenced at the same time, but have previously been published as part of GSE50515. There were at least 3 replicates from biological samples.
Sex Differences in Drosophila Somatic Gene Expression: Variation and Regulation by doublesex.
Sex, Specimen part, Cell line, Subject
View SamplesNucleosomes are the basic unit of chromatin. Nucleosome positioning (NP) plays a key role in transcriptional regulation and other biological processes. To better understand NP we used MNase-seq to investigate changes that occur as human embryonic stem cells (hESCs) transition to nascent mesoderm and then to smooth muscle cells (SMCs). Compared to differentiated cell derivatives, nucleosome occupancy at promoters and other notable genic sites, such as exon/intron junctions and adjacent regions, in hESCs shows a stronger correlation with transcript abundance and is less influenced by sequence content. Upon hESC differentiation, genes being silenced, but not genes being activated, display a substantial change in nucleosome occupancy at their promoters. Genome-wide, we detected a shift of NP to regions of higher G+C content as hESCs differentiate to SMCs. Notably, genomic regions with higher nucleosome occupancy harbor twice as many GC changes but fewer than half AT changes, compared to regions with lower nucleosome occupancy. Finally, our analysis indicates that the hESC genome is not rearranged and has a sequence mutation rate resembling normal human genomes. Our study reveals another unique feature of hESC chromatin, and sheds light on the relationship between nucleosome occupancy and sequence G+C content.
Nucleosome positioning changes during human embryonic stem cell differentiation.
Specimen part, Cell line
View SamplesPurpose: The goals of this study are to compare the effects of 5% and 20% oxygen culture on human embryonic stem cells, inlcuding the impact on their transcriptomes. Overall design: mRNA profiles of two human embryonic stem cell lines (MEL1 and MEL2) cultured long term at 5% and 20% oxygen.
Oxygen Regulates Human Pluripotent Stem Cell Metabolic Flux.
Cell line, Subject
View SamplesTo gain insight into the molecular underpinnings of the post-mating response that depend on the germline, we independently assess the contribution of the female germline and the male germline on gene expression changes in head tissues of females using RNA-seq. Overall design: mRNA profiles of head tissues in virgin and mated (1 and 3 days post-mating) females that either have or are lacking a germline and females mated to males that either have or are lacking a germline. Samples were generated in triplicate and sequenced on an Illumina Genome Analyzer IIx.
The <i>Drosophila</i> Post-mating Response: Gene Expression and Behavioral Changes Reveal Perdurance and Variation in Cross-Tissue Interactions.
Sex, Age, Subject
View SamplesReprogrammed somatic cells offer a valuable source of pluripotent cells that have the potential to differentiate into many cells types and provide a new tool for regenerative medicine. In the present study we differentiated induced pluripotent stem cells (iPS cells) into hepatic cells. We first showed that mouse iPS cells could from a complete liver in mouse embryo (E14.5) including hepatocytes, endothelial cells, sinusoidal cells and resident macrophages. We then designed a highly efficient hepatocyte differentiation protocol using defined factors on human embryonic stem cells (ES cells). This protocol was found to generate more than 80% albumin expressing cells that show hepatic functions and express most of liver genes as shown by microarray analyses. Similar results were obtained when human iPS cells were induced to differentiate following the same procedure.
Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Linking DNA methyltransferases to epigenetic marks and nucleosome structure genome-wide in human tumor cells.
Specimen part, Cell line
View SamplesWe used microarrays to profile gene expression of NCCIT cells to study the link between epigenetic modifications and gene transcription.
Linking DNA methyltransferases to epigenetic marks and nucleosome structure genome-wide in human tumor cells.
Specimen part
View SamplesChoroid plexus carcinomas (CPC) are poorly understood and frequently lethal brain tumors with minimal treatment options. Using a new mouse model of the disease and a large cohort of human CPCs [GSE60892; GSE60899], we performed a cross-species, genome-wide search for novel oncogenes within syntenic regions of chromosome gain. TAF12, NFYC and RAD54L, co-located on human chromosome 1p32-35.3 and mouse chromosome 4qD1-D3, were identified as oncogenes that are gained in tumors in both species and required to initiate and progress the disease in mice. TAF12 and NFYC are transcription factors that regulate the epigenome, while RAD54L plays a central role in DNA repair. Our data identify a group of concurrently gained, novel oncogenes that cooperate in the formation of CPC and unmask potential new avenues for therapy.
Cross-Species Genomics Identifies TAF12, NFYC, and RAD54L as Choroid Plexus Carcinoma Oncogenes.
No sample metadata fields
View Samples