A prevalent hypothesis for the cell-to-cell coordination of the phenomena of early development is that a defined mixture of different mRNA species at specific abundances in each cell determines fate and behavior. With this dataset we explore this hypothesis by quantifying the abundance of every mRNA species in every individual cell of the early C. elegans embryo, for which the exact life history and fate is precisely documented. Overall design: Embryos of the 1-, 2-, 4-, 8- and 16-cell stage were dissected into complete sets of single cells, and each cell from each set was sequenced individually using SMARTer technology. 5-9 replicates were generated for each stage. Most cell identities were unknown upon sequencing, but were deduced from by their transcriptomes post hoc.
A Transcriptional Lineage of the Early C. elegans Embryo.
Specimen part, Subject
View SamplesWe sequenced amplified mRNA from 20 pooled AB and 20 pooled P1 blastomeres hand isolated from 2-cell stage C. elegans embryos three replicates each. Overall design: Transcriptome profiles of each blastomere at the 2-cell stage of the C. elegans early embryo.
Asymmetric transcript discovery by RNA-seq in C. elegans blastomeres identifies neg-1, a gene important for anterior morphogenesis.
Specimen part, Cell line, Subject
View SamplesMuscle biopsies taken from vastus lateralis muscle of 30 normal subjects and 19 FSHD subjects (see PubMed ID 17151338)
Expression profile of FSHD supports a link between retinal vasculopathy and muscular dystrophy.
No sample metadata fields
View SamplesT2 progenies of two transgenic lines overexpressing ERF transcription factor WIN1 were grown on soil in parallel under identical conditions. mRNA was extracted from pooled leaves from multiple plants of each line for the microarray experiement.
WIN1, a transcriptional activator of epidermal wax accumulation in Arabidopsis.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy.
Sex, Specimen part
View SamplesWe are using genome-wide ChIP-seq with isoform-specific antibodies and chromatin from select tissues of mice challenged with different dietary conditions that enrich for specific SREBPs.
Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy.
Sex, Specimen part
View SamplesMyotonic dystrophy type 1 (DM1) is an RNA dominant disease in which mutant transcripts containing an expanded CUG repeat (CUGexp) cause muscle dysfunction by interfering with biogenesis of other mRNAs. The toxic effects of mutant RNA are mediated partly through sequestration of splicing regulator Muscleblind-like 1 (Mbnl1), a protein that binds to CUGexp RNA. A gene that is prominently affected encodes chloride channel 1 (Clcn1), resulting in hyperexcitability of muscle (myotonia). To identify DM1-affected genes and study mechanisms for dysregulation, we performed global mRNA profiling in transgenic mice that express CUGexp RNA, as compared to Mbnl1 knockout and Clcn1 null mice. We found that the majority of changes induced by CUGexp RNA in skeletal muscle can be explained by reduced activity of Mbnl1, including many changes that are secondary to myotonia. The pathway most affected comprises genes involved in calcium signaling and homeostasis. Some effects of CUGexp RNA on gene expression are caused by abnormal alternative splicing or downregulation of Mbnl1-interacting mRNAs. However, several of the most highly dysregulated genes showed altered transcription, as indicated by parallel changes of the corresponding premRNAs. These results support the idea that trans-dominant effects of CUGexp RNA on gene expression in this transgenic model may occur at the level of transcription, RNA processing, and mRNA decay, and are mediated mainly but not entirely through sequestration of Mbnl1.
Transcriptional and post-transcriptional impact of toxic RNA in myotonic dystrophy.
Sex, Age
View SamplesGene expression from bone-marrow drived macrophages of WT and SREBP-1a deficient mice
Linking lipid metabolism to the innate immune response in macrophages through sterol regulatory element binding protein-1a.
No sample metadata fields
View SamplesSubstantial evidence implicates IGF-I signaling in the development and progression of breast cancer. To identify transcriptional targets of IGF action in breast cancer cells, we performed gene expression profiling (>22,000 RNA transcripts) of IGF-I-stimulated MCF-7 cells, a well characterized breast cancer cell line that is highly responsive to IGFs. We defined an IGF-I gene signature pattern of hundreds of genes either up-regulated or down-regulated at both 3 and 24 hrs in vitro. After removing genes considered generic to cell proliferation, the signature was examined in four different public profile datasets of clinical breast tumors (representing close to 1000 patients), as well as in profile datasets of experimental models for various oncogenic signaling pathways. Genes with early and sustained regulation by IGF-I were highly enriched for transcriptional targets of the estrogen, Ras, and PI3K/Akt/mTOR pathways. The IGF-I signature appeared activated in most estrogen receptor-negative (ER-) clinical breast tumors and in a substantial subset (~25%) of ER+ breast tumors. Patients with tumors showing activation of the IGF-I signature tended to have a shorter time to disease recurrence (including patients not receiving adjuvant therapy), both when considering all patients and the subset of ER+ patients. We found evidence for cross-talk and common transcriptional endpoints between the IGF-I and estrogen systems. Our results support the idea that the IGF-I pathway is one mechanism by which breast tumors may acquire hormone independence and a more aggressive phenotype.
Insulin-like growth factor-I activates gene transcription programs strongly associated with poor breast cancer prognosis.
No sample metadata fields
View SamplesTo investigate molecular mechanisms of resistance, we used two different in vivo xenograft models of estrogen receptor-positive (ER+) breast cancer, with or without HER2 over-expression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: continued estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the EGFR tyrosine kinase inhibitor gefinitinib (G). Another group received ED plus the antiestrogen fulvestrant (MCF7 wt only). Tumors with acquired or de novo resistance to these endocrine therapies were profiled for mRNA expression using Affymetrix Genechip arrays.
Development of resistance to targeted therapies transforms the clinically associated molecular profile subtype of breast tumor xenografts.
No sample metadata fields
View Samples