This SuperSeries is composed of the SubSeries listed below.
An alternative pluripotent state confers interspecies chimaeric competency.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
Specimen part
View SamplesMammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell type-specific gene expression programs; however, the potential that there are pre-established enhancers in different functional classes that permit alternative signal-dependent transcriptional responses has remained unexplored. Here we present evidence that cell lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), acting at structurally- and functionally-distinct classes of pre-established enhancers, thus licensing specific signal-activated responses while restricting others. Consequently, FoxA1 down-regulation, an unfavorable prognostic sign in advanced prostate tumors, causes a massive switch in AR binding from one functional class of enhancers to another, with a parallel switch in levels of enhancer-templated non-coding RNAs (eRNAs) revealed by the global run-on assay (GRO-seq), which documents the dramatic reprogramming of the hormonal response. The molecular basis for this switch lies in the release of FoxA1-mediated restriction of AR binding to the new enhancer class with no apparent nucleosome remodeling, which is required for stimulating their eRNA transcription and/or enhancing enhancer:promoter looping and gene activation. Together, these findings reveal a large repository of pre-determined enhancers in the human genome that can be dynamically tuned to induce their transcription and activation of alternative gene expression programs, which may underlie many sequential gene expression events in development or during disease progression.
Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA.
Specimen part
View SamplesHere we show that by simple modulation of extrinsic signaling pathways, a new class of pluripotent stem cells, referred to as intrinsic state-epiblast stem cells (IS-EPIs), could be efficiently derived from different stages of the early embryo. IS-EPIs share features of primed pluripotency yet are distinct from EpiSCs in their molecular characteristics and ability to colonize post-implantation embryos. We performed Microarray analysis and compared global gene expression pattern among amplified RNA samples from ESCs, EpiSCS, IS-EPIs as well as in vivo isolated Epiblasts.
An alternative pluripotent state confers interspecies chimaeric competency.
Specimen part
View SamplesLong non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and chromatin modifications, with important functions in development and disease. Here we sought to identify and functionally characterize lncRNAs critical for vascular vertebrate development with significant conservation across species. Genome-wide transcriptomic analyses during human vascular lineage specification enabled the identification of three conserved novel lncRNAs: TERMINATOR, ALIEN and PUNISHER that are specifically expressed in pluripotent stem cells, mesoderm and endothelial cells, respectively. Gene expression profiling, alongside RNA immunoprecipitation coupled to mass spectrometry, revealed a wide range of new molecular networks and protein interactors related to post-transcriptional modifications for all three lncRNAs. Functional experiments in zebrafish and murine embryos, as well as differentiating human cells, confirmed a developmental-stage specific role for each lncRNA during vertebrate development. The identification and functional characterization of these three novel non-coding provide a comprehensive transcriptomic roadmap and shed new light on the molecular mechanisms underlying human vascular development.
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
Specimen part
View SamplesIn this study, we compared the genome-wide transcriptome of mouse and human placentas across gestation to identify species-specific signatures of early development. We also compared human placental signatures to purified primary cytotrophoblasts (CTB) isolated from placentae at different gestational age.
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
No sample metadata fields
View SamplesIn this study, we compared the genome-wide transcriptome of mouse and human placentas across gestation to identify species-specific signatures of early development. We also compared human placental signatures to purified primary cytotrophoblasts (CTB) isolated from placentae at different gestational age.
Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development.
No sample metadata fields
View SamplesCerebral palsy is primarily an upper motor neuron disease that results in a spectrum of progressive movement disorders. Secondary to the neurological lesion, muscles from patients with cerebral palsy are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in cerebral palsy is a response to aberrant neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response to cerebral palsy using microarrays and correlating the transcriptional data with functional measures. Hamstring biopsies from gracilis and semitendinosus muscles were obtained from a cohort of patients with cerebral palsy (n=10) and typically developing patients (n=10) undergoing surgery. Affymetrix HG-U133A 2.0 chips (n=40) were used and expression data was verified for 6 transcripts using quantitative real-time PCR, as well as for two genes not on the microarray. Chips were clustered based on their expression and those from patients with cerebral palsy clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n=1,398). Significantly altered genes were analyzed for over-representation among gene ontologies, transcription factors, pathways, microRNA and muscle specific networks. These results centered on an increase in extracellular matrix expression in cerebral palsy as well as a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and novel therapies.
Transcriptional abnormalities of hamstring muscle contractures in children with cerebral palsy.
Sex, Age, Disease, Subject
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