Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA282971 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcription Factor TLX1 Controls Retinoic Acid Signaling to Ensure Spleen Development
| PRJNA322247 | ENA
Project description:Transcription Factor TLX1 Controls Retinoic Acid Signaling to Ensure Spleen Development [ChIP-Seq]
| PRJNA322248 | ENA
Project description:The molecular mechanisms underlying asplenia, a condition often associated with overwhelming infections remain largely unknown. During spleen development, the transcription factor TLX1 controls morphogenesis and organ expansion, and loss of it causes spleen agenesis. However, the downstream signaling pathways that are deregulated in the absence of TLX1 are mostly unknown. Herein, we demonstrate that loss of Tlx1 in the splenic mesenchyme causes increased retinoic acid (RA) signaling. Increased RA activity causes premature differentiation of the splenic mesenchyme and reduced vasculogenesis of the splenic anlage. Moreover, excess or deficiency in RA signaling, as observed in Cyp26b1 or Rdh10 mutants respectively, also results in spleen growth arrest. Genome-wide analysis revealed that TLX1 binds RA-associated genes through the AP-1 site and cooperates with the AP-1 family transcription factors to regulate transcription. Pharmacological inhibition of RA signaling partially rescues the spleen defect. These findings establish the critical role of TLX1 in controlling RA metabolism, and provide novel mechanistic insights into the molecular determinants underlying congenital asplenia.
2016-07-01 | GSE68519 | GEO
Project description:The molecular mechanisms underlying asplenia, a condition often associated with overwhelming infections remain largely unknown. During spleen development, the transcription factor TLX1 controls morphogenesis and organ expansion, and loss of it causes spleen agenesis. However, the downstream signaling pathways that are deregulated in the absence of TLX1 are mostly unknown. Herein, we demonstrate that loss of Tlx1 in the splenic mesenchyme causes increased retinoic acid (RA) signaling. Increased RA activity causes premature differentiation of the splenic mesenchyme and reduced vasculogenesis of the splenic anlage. Moreover, excess or deficiency in RA signaling, as observed in Cyp26b1 or Rdh10 mutants respectively, also results in spleen growth arrest. Genome-wide analysis revealed that TLX1 binds RA-associated genes through the AP-1 site and cooperates with the AP-1 family transcription factors to regulate transcription. Pharmacological inhibition of RA signaling partially rescues the spleen defect. These findings establish the critical role of TLX1 in controlling RA metabolism, and provide novel mechanistic insights into the molecular determinants underlying congenital asplenia. Samples: 3 replicates of E13.5 spleens from Tlx1 heterozygous embryos were compared to 3 replicates of E13.5 spleens from Tlx1 homozygous embryos
2016-07-01 | E-GEOD-68519 | biostudies-arrayexpress
Project description:The molecular mechanisms that underlie spleen development and congenital asplenia, a condition linked to increased risk of overwhelming infections, remain largely unknown. The transcription factor TLX1 controls cell fate specification and organ expansion during spleen development, and Tlx1 deletion causes asplenia in mice. Deregulation of TLX1 expression has recently been proposed in the pathogenesis of congenital asplenia in patients carrying mutations of the gene-encoding transcription factor SF-1. Herein, we have shown that TLX1-dependent regulation of retinoic acid (RA) metabolism is critical for spleen organogenesis. In a murine model, loss of Tlx1 during formation of the splenic anlage increased RA signaling by regulating several genes involved in RA metabolism. Uncontrolled RA activity resulted in premature differentiation of mesenchymal cells and reduced vasculogenesis of the splenic primordium. Pharmacological inhibition of RA signaling in Tlx1-deficient animals partially rescued the spleen defect. Finally, spleen growth was impaired in mice lacking either cytochrome 26B1 (Cyp26b1), which results in excess RA, or retinol dehydrogenase 10 (Rdh10), which results in RA deficiency. Together, these findings establish TLX1 as a critical regulator of RA metabolism and provide mechanistic insight into the molecular determinants of human congenital asplenia.
2016-07-01 | GSE81660 | GEO
Project description:The molecular mechanisms that underlie spleen development and congenital asplenia, a condition linked to increased risk of overwhelming infections, remain largely unknown. The transcription factor TLX1 controls cell fate specification and organ expansion during spleen development, and Tlx1 deletion causes asplenia in mice. Deregulation of TLX1 expression has recently been proposed in the pathogenesis of congenital asplenia in patients carrying mutations of the gene-encoding transcription factor SF-1. Herein, we have shown that TLX1-dependent regulation of retinoic acid (RA) metabolism is critical for spleen organogenesis. In a murine model, loss of Tlx1 during formation of the splenic anlage increased RA signaling by regulating several genes involved in RA metabolism. Uncontrolled RA activity resulted in premature differentiation of mesenchymal cells and reduced vasculogenesis of the splenic primordium. Pharmacological inhibition of RA signaling in Tlx1-deficient animals partially rescued the spleen defect. Finally, spleen growth was impaired in mice lacking either cytochrome 26B1 (Cyp26b1), which results in excess RA, or retinol dehydrogenase 10 (Rdh10), which results in RA deficiency. Together, these findings establish TLX1 as a critical regulator of RA metabolism and provide mechanistic insight into the molecular determinants of human congenital asplenia. We performed ChIP-sequencing for Hox11 rep1 and rep2 in eSMC untreated cells.
2016-07-01 | E-GEOD-81660 | biostudies-arrayexpress
Project description:Genome-wide expression studies were performed on dermal fibroblasts from Sotos syndrome patients with a confirmed NSD1 abnormality and compared with age-sex matched controls. We used microarrays to detect differentially expressed genes in Sotos syndrome patients and performed a global test with the aim to map NSD1 within a signaling transduction pathway. Dermal fibroblasts were obtained from nine Sotos syndrome patients and nine controls. Since NSD1 is a co-factor of the retinoic acid receptor, cultures were performed both in the presence and absence of retinoic acid.
2014-02-06 | E-GEOD-27200 | biostudies-arrayexpress
Project description:The morphologic changes of neuroepithelial cells, and their interactions with surrounding cells, are fundamental to primary neurulation and are a function of several timed signaling gradients. Retinoic acid administration at fetal day E10 induces neural tube defects in 84.2% of rat pups. Negative selection using A2B5 and E-NCAM has been validated for isolation of neuroepithelial cells for culture. Here we report the isolation and analysis of the fundamental actors in primary neurulation by flow cytometry with CD147 positive selection followed by whole transcriptome analysis of this purified population via microarray enhanced with the ERCC RNA internal controls. Comparison of the gene expression in Retinoic acid exposed versus wild-type isolates shows excellent correspondence to known neural tube defect genes. Analysis of transcription factor binding sites in regulatory regions of differentially expressed genes, implicates a binding site “cross-roads” where improper signaling through a multitude of pathways could potentially elicit neural tube defects.
2016-12-01 | GSE74221 | GEO
Project description:Dietary vitamin A is metabolized into bioactive retinoic acid in vivo and regulates the development of many embryonic tissues. Retinoic acid signaling is active in the oral ectoderm-derived tissues of the neuroendocrine system, but its role there has not yet been fully explored. We show here that retinoic acid signaling is active during pituitary organogenesis and dependent on the pituitary transcription factor Prop1. Prop1-mutant mice show reduced expression of the aldehyde dehydrogenase gene Aldh1a2, which metabolizes the vitamin A-intermediate retinaldehyde into retinoic acid. In order to elucidate the specific function of RA signaling during neuroendocrine development, we studied a conditional deletion of Aldh1a2 and a dominant-negative mouse model of inhibited retinoic acid signaling during pituitary organogenesis. These models partially phenocopy Prop1-mutant mice by exhibiting embryonic pituitary dysmorphology and reduced hormone expression, especially of thyroid-stimulating hormone. These findings establish the critical role of retinoic acid in embryonic pituitary stem cell progression to differentiated hormone cells and raise the question of gene-by-environment interactions as contributors to pituitary development and disease.
2020-02-26 | GSE142074 | GEO
Project description:To identify downstream transcription factors induced by retinoic acid, we stimulated SFZ cells with 10 μM retinoic acid for 24 hours and performed microarray analysis.
2018-12-17 | GSE107069 | GEO