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 SamplesEnd stage renal disease (ESRD) is associated with hyperplastic-cystic remodelling of the kidneys (ARCD) and increased rate of kidney tumours. Using the Affymetrix oligoarray, we have established the gene expression signature of ESRD/ARCD kidneys and compared to those of normal kidneys and of distinct types of renal tumours.
Gene expression profiling of chromophobe renal cell carcinomas and renal oncocytomas by Affymetrix GeneChip using pooled and individual tumours.
No sample metadata fields
View SamplesExpression data from HeLa cells treated with V-ATPase inhibitors or with desoxyferramine compared to HeLa treated with DMSO or medium with low LDL
Inhibition of iron uptake is responsible for differential sensitivity to V-ATPase inhibitors in several cancer cell lines.
Cell line
View SamplesTissues from the eye primordia, lateral endoderm, and posterior
Generation of functional eyes from pluripotent cells.
No sample metadata fields
View SamplesXenopus laevis embryos were injected with mRNA for EFTFs at 2-cell stage. Animal caps collected at stage 9, cultured to the equivalent of stage 15 and RNA extracted. Four biological replicates of the EFTF-injected and GFP-injected (control) caps were used to profile transcript expression patterns using Affymetrix Xenopus Laevis GeneChip microarrays.
Generation of functional eyes from pluripotent cells.
No sample metadata fields
View SamplesSCOPE: We investigated whether a novel dietary intervention consisting of an every-other-week calorie-restricted diet could prevent nonalcoholic fatty liver disease (NAFLD) development induced by a medium-fat (MF) diet.
A weekly alternating diet between caloric restriction and medium fat protects the liver from fatty liver development in middle-aged C57BL/6J mice.
Sex, Age
View SamplesBackground & Aims: In this study, we investigated metabolic and molecular effects of weekly intervening 30% calorie restriction on long term natural progression of non-alcoholic fatty liver disease (NAFLD), which was induced by a medium fat diet.
A weekly alternating diet between caloric restriction and medium fat protects the liver from fatty liver development in middle-aged C57BL/6J mice.
Sex, Age, Specimen part, Treatment
View SamplesBRUCE was identified as a novel positive regulator of autophagy. By analyzing changes in mRNA levels, we wanted to determine whether BRUCE regulates autopahgy on a trancscriptional level. Overall design: Examination of changes in total mRNA levels comparing control (shRenilla) and BRUCE knockdown (shBruce) cells in full medium (FM) and starvation medium (Starv)
The IAP family member BRUCE regulates autophagosome-lysosome fusion.
Specimen part, Subject
View SamplesGene expression profiling by high-throughput sequencing reveals qualitative and quantitative changes in RNA species at steady-state but obscures the intracellular dynamics of RNA transcription, processing and decay. We developed thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAM-seq), an orthogonal chemistry-based epitranscriptomics-sequencing technology that uncovers 4-thiouridine (s4U)-incorporation in RNA species at single-nucleotide resolution. In combination with well-established metabolic RNA labeling protocols and coupled to standard, low-input, high-throughput RNA sequencing methods, SLAM-seq enables rapid access to RNA polymerase II-dependent gene expression dynamics in the context of total RNA. When applied to mouse embryonic stem cells, SLAM-seq provides global and transcript-specific insights into pluripotency-associated gene expression. We validated the method by showing that the RNA-polymerase II-dependent transcriptional output scales with Oct4/Sox2/Nanog-defined enhancer activity; and provides quantitative and mechanistic evidence for transcript-specific RNA turnover mediated by post-transcriptional gene regulatory pathways initiated by microRNAs and N6-methyladenosine. SLAM-seq facilitates the dissection of fundamental mechanisms that control gene expression in an accessible, cost-effective, and scalable manner. Overall design: Wildtype mouse embryonic stem cells (mES cells) were subjected to s4U metabolic RNA labeling for 24 h (pulse, 100 µM s4U), followed by washout (chase) using non-thiol-containing uridine. Total RNA was prepared at various time points along the chase (0h, 0.5h, 1h, 3h, 6h, 12h, and 24h). Total RNA was then subjected to alkylation and mRNA 3' end sequencing library preparation (QuantSeq, Lexogen).
Quantification of experimentally induced nucleotide conversions in high-throughput sequencing datasets.
Specimen part, Treatment, Subject
View SamplesRenal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e. distal convoluted tubule (DCT) and connecting tubule (CNT) and, the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, alphaENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function.
Molecular clock is involved in predictive circadian adjustment of renal function.
Sex, Specimen part
View Samples