We demonstrate that PKA signalling drives zonal conversion within adult adrenocortical lineage in a sexually dimorphic manner. Our data establish that Prkar1a genetic ablation (leading to constitutive PKA activation) in the adult adrenocortical lineage leads to endocrine hyperactivity and accelerates adrenal cortex renewal. This results in increased zona fasciculata differentiation and final conversion into reticularis-like zone. This phenomenon relies partly on sex-dependent mechanisms of cortical renewal, on which the male androgenic milieu exerts a repressive action through induction of WNT signalling, which in turn antagonizes PKA signalling and cortical cell turnover.
PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal.
Sex, Specimen part
View SamplesEzh2 encodes the catalytic subunit of the polycomb repressive complex 2 epigenetic regulator. Its ablation in the adrenal cortex results in profound alterations of adrenal homeostasis.
Steroidogenic differentiation and PKA signaling are programmed by histone methyltransferase EZH2 in the adrenal cortex.
Sex, Age, Specimen part
View SamplesLiver undergoes both size increase and differentiation during postnatal period, which in mice is approximately first 30 days. The mechanisms of simultaneous postnatal liver cell proliferation and maturation are not clear. In these experiments, role of yes associated protein (Yap), the downstream effector of Hippo Kinase signaling pathway was investigated.
Yes-associated protein is involved in proliferation and differentiation during postnatal liver development.
Specimen part
View SamplesWe sought to elucidate the molecular mechanisms whereby LIN28B functions by comparing the gene expression profile of cells constitutively expressing LIN28B to empty vector controls.
LIN28B promotes colon cancer progression and metastasis.
Disease, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
microRNAs Involved in Regulating Spontaneous Recovery in Embolic Stroke Model.
Sex, Specimen part
View SamplesTo date, miRNA and mRNA expression studies on cerebral ischemia in both human and animal models have focused mainly on acute phase of ischemic stroke. In this study, we present the roles played by microRNAs in the spontaneous recovery phases in cerebral ischemia using rodent stroke models.
microRNAs Involved in Regulating Spontaneous Recovery in Embolic Stroke Model.
Sex, Specimen part
View SamplesWe report the transcriptional response of the zebrafish digestive organs to an acute high-fat feed using RNASeq analysis and highlight the changes in gene expression involved in the synthesis, storage, and dispersal of lipids. These key physiological responses to a high-fat meal all stem from the endoplasmic reticulum (ER), where lipids are formed and assigned to their fates. Overall design: A feeding time course was undertaken with 6.5-dpf larval zebrafish. Triplicate samples were independently prepared from pairwise crosses fed either high-fat or low-fat food. 5% egg yolk emulsion (high-fat) feeds and 10% egg white (low-fat) feeds were prepared. At the appropriate time points, digestive organs (intestine, liver, pancreas) were dissected from 10 anesthetized larval zebrafish. Unfed controls were used to determine a transcriptional baseline.
Endoplasmic Reticulum Lipid Flux Influences Enterocyte Nuclear Morphology and Lipid-dependent Transcriptional Responses.
No sample metadata fields
View SamplesTranscription factor complexes bind to regulatory sequences of genes, providing a system of individual expression regulation. Targets of distinct transcription factors usually map throughout the genome, without clustering. Nevertheless, highly and weakly expressed genes do cluster in separate chromosomal domains with an average size of 80 to 90 genes. We therefore asked whether, besides transcription factors, an additional level of gene expression regulation exists that acts on chromosomal domains. Here we show that identical green fluorescent protein (GFP) reporter constructs integrated at 90 different chromosomal positions determined by sequencing, obtain expression levels that correspond to the activity of the domains of integration. These domains are about 80 genes long and can exert an effect of up to 8-fold on the expression of integrated genes. 3D-FISH shows that active domains of integration have a more open chromatin structure than integration domains with weak activity. These results reveal a novel domain-wide regulatory mechanism that, together with transcription factors, exerts a dual control over gene transcription.
Domain-wide regulation of gene expression in the human genome.
No sample metadata fields
View SamplesRNA-Sequencing analysis of 18 papillary thyroid carcinoma biopsies and of 4 healthy donors'' thyroids. In this analysis we assessed differential gene expression and investigated the mutational landscape in this tumor type. Analysis of gene fusion was also performed, leading to the identification of a novel chimeric transcript, potential driver in tumor initiation. Overall design: Total RNA isolated from 18 papillary thyroid carcinoma biopsies and 4 healthy donors'' thyroids.
New somatic mutations and WNK1-B4GALNT3 gene fusion in papillary thyroid carcinoma.
No sample metadata fields
View SamplesThe extremely low efficiency of human embryonic stem cell (hESC) derivation using somatic cell nuclear transfer (SCNT) limits potential application. Blastocyst formation from human SCNT embryos occurs at a low rate and with only some oocyte donors. We previously showed in mice that reduction of histone H3 lysine 9 trimethylation (H3K9me3) through ectopic expression of the H3K9me3 demethylase Kdm4d greatly improves SCNT embryo development. Here we show that overexpression of a related H3K9me3 demethylase KDM4A improves human SCNT, and that, as in mice, H3K9me3 in the human somatic cell genome is an SCNT reprogramming barrier. Overexpression of KDM4A significantly improves the blastocyst formation rate in human SCNT embryos by facilitating transcriptional reprogramming, allowing derivation of NTESCs from all oocyte donors tested using adult AMD patient somatic nuclei donors. This conserved mechanistic insight has potential applications for improving SCNT in a variety of contexts, including regenerative medicine. Overall design: Here we perform RNA-seq based transcriptome profiling in human Donor (fibroblast cells), in vitro fertilized embryos at 8-cell stages (IVF_8Cell), somatic cell nuclear transfer embryos at 8-cell stages (SCNT_8Cell), SCNT assisted by KDM4A 8-cell embryos (SCNT_KDM4A_8Cell). Besides, we also perform RNA-seq in Control human ES cells (CTR_hES) and SCNT assisted by KDM4A derived human ES cells (NTK) with duplicates.Â
Histone Demethylase Expression Enhances Human Somatic Cell Nuclear Transfer Efficiency and Promotes Derivation of Pluripotent Stem Cells.
No sample metadata fields
View Samples