Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA135623 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The corticomedullary osmotic gradient between renal cortex and medulla induces a specific spatial gene expression pattern. The factors that control these differences are not fully addressed. The hypertonic environment leads to activation of the nuclear factor of activated T-cells 5 (NFAT5), which regulates the expression of osmoprotective genes. While NFAT5 function under hypertonic conditions has been extensively studied, its contribution to basal gene 28 regulation remains incompletely understood. We used murine principal kidney cortical collecting duct (mpkCCD) cells and induced functional deletion of NFAT5 and performed gene expression profiling to identify genes that are differentially expressed under isotonic and hypertonic cell culture conditions. Hypertonic stress induced extensive transcriptional changes in control cells, which were markedly altered in NFAT5-deficient cells. Furthermore, the comparison of the mpkCCD transcriptomes with gene expression profiles from renal cortex and inner medulla of control and principal cell-specific NFAT5 knockout mice revealed partial overlap in hypertonicity-associated and NFAT5-dependent gene expression patterns. In both conditions, the expression of known NFAT5 target genes, like Aqp2 or Ranbp3l, was downregulated. These findings support the use of mpkCCD cells as a complementary model to study NFAT5-associated gene regulation under controlled in vitro conditions.
2026-06-25 | GSE326713 | GEO
Project description:RNA sequencing of nucleus pulposus cells transduced with control or TonEBP shRNA and cultured under hypertonic conditions
2016-11-08 | GSE86552 | GEO
Project description:TonEBP is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Out of over 100 potentially new TonEBP regulated genes, we selected 7 for further analyses and found that their expression was all dependent on TonEBP. RNA interference experiments showed that some of these genes – asporin, insulin-like growth factor-binding protein 5 and 7, and an extracellular lysophosphlipase D – plus Hsp70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation. Quadruplicate samples were collected for each condition and then pooled into a single sample for hybridization to microarrays.
2010-12-10 | E-GEOD-25816 | biostudies-arrayexpress
Project description:TonEBP is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Out of over 100 potentially new TonEBP regulated genes, we selected 7 for further analyses and found that their expression was all dependent on TonEBP. RNA interference experiments showed that some of these genes – asporin, insulin-like growth factor-binding protein 5 and 7, and an extracellular lysophosphlipase D – plus Hsp70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation.
2010-12-10 | GSE25816 | GEO
Project description:Homeostatic control of intracellular ionic strength is essential for protein, organelle and genome function, yet mechanisms that sense and enable adaptation to ionic stress remain poorly understood in animals. We find that the transcription factor NFAT5 directly senses solution ionic strength using a C-terminal intrinsically disordered region. Both in intact cells and in a purified system, NFAT5 forms dynamic, reversible biomolecular condensates in response to increasing ionic strength. This self-associative property, conserved from insects to mammals, allows NFAT5 to accumulate in the nucleus and activate genes that restore cellular ion content. Mutations that reduce condensation or those that promote aggregation both reduce NFAT5 activity, highlighting the importance of optimally tuned associative interactions. To investigate the composition of NFAT5 condensates in response to hypertonic stress, proteins in close proximity of NFAT5 were identified using a variant of NFAT5 fused to TurboID as bait. Hypertonic stress increases NFAT5 proximity to protein complexes belonging to the GO gene sets of “transcription coactivator activity” and “positive regulation of DNA templated transcription initiation.” Closer inspection revealed that the association between NFAT5 and two transcriptional co-activators (the mediator complex and BRD4) and RNAPII itself increased in response to hypertonic stress.
2025-04-17 | PXD052591 | Pride
Project description:NFAT5 is transcription factor that regulates gene expression in response to hypertonic stress. Here we profile NFAT5 occupancy before and hour following hypertonic stress in mouse inner medulla collecting duct cells, as resource to localize sites with tonicity depend chromatin occupancy. In addition, we test the occupancy of the active histone mark H3K27ac and the repressive mark H3K27me3.
2026-04-10 | GSE302740 | GEO
Project description:Tonicity-Responsive Enhancer-Binding Protein (NFAT5), also known as Tonicity-Responsive Enhancer Binding Protein (TonEBP), is a important transcription factor in the regulation of osmoprotective and inflammatory genes. NFAT5 has been reported to regulate the pathological processes of inflammatory and autoimmune disorders. Our data provides a insight to the gene expression in NFAT5 deficiency BV2 microglia cells, which NFAT5 knocked down by sh-RNA.
2024-02-15 | GSE249968 | GEO
Project description:ATAC-seq profiling of Nfat5 KO and wild type macrophages derived from bone marrow (primary cells), treated or not with Lipopolysaccharide (LPS).
2021-06-09 | GSE111476 | GEO
Project description:Adaptation of C. elegans to hypertonic environments involves the accumulation of the organic osmolyte glycerol via transcriptional upregulation of the glycerol biosynthestic enzyme gpdh-1. A number of mutants, termed osmotic stress resistant (osr) mutants, have been identified. osr mutants cause constitutive upregulation of gpdh-1 and confer extreme resistance to hypertonicity. We tested the hypothesis that osr mutants broadly activate a gene expression program normally activated by osmotic stress in wild type animals using Affymterix microarray analysis of the hypertonic stress response in wild type animals and of constituitive gene expression changes in five osr mutants. Experiment Overall Design: Young adult C. elegans were exposed to hypertonic growth plates for varying times prior to RNA extraction and hybridization on Affymetrix microarrays. Since we wished to separate direct response from secondary responses to osmotic stress, we collected worms following short term exposures to hypertonic conditions (15 minutes and 1 hour) and after long term exposure to hypertonic conditions (6 hours or a full generation of growth under hypertonic conditions). We also collected young adults from the osr mutants osm-7, osm-8, osm-11, dpy-9, and dpy-10 for microarray analysis. These mutants were grown under isotonic conditions to determine whether that constitutively activate genes normally regulated by hypertonic stress in wild type animals.
2009-12-14 | E-GEOD-19310 | biostudies-arrayexpress
Project description:Chronic hypoxic stress stimulates lung endothelial cells to promote vascular remodeling processes, which - in the long run - increase the resistance of pulmonary arteries. While several molecular determinants promoting these maladaptive changes have been delineated, their transcriptional regulation is not well studied. In this context, we revealed that hypoxia activates nuclear factor of activated T-cells 5 (NFAT5/TonEBP) in murine lung endothelial cells (MLECs) - a transcription factor that regulates the adjustment of the cellular transcriptome to cope with osmotic, biomechanical or metabolic environmental stressors. Here, we studied the functional relevance of NFAT5 for the control of endothelial hypoxic stress responses in the lung. Genetic ablation of Nfat5 in endothelial cells did not evoke any obvious phenotypic alterations under normoxia. However, microarray-based transcriptome analyses of lung tissue revealed significant alterations 7 but not 21 days after exposure to normobaric hypoxia (10% O2).
2024-08-08 | GSE230053 | GEO