Wnt5a-deficient vs. wild-type E18 liver
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE41803 | GEO | 2013/02/07
SECONDARY ACCESSION(S): PRJNA178218
REPOSITORIES: GEO
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Project description:Transcriptional profiling of E18.5 livers derived from Wnt5a-deficient (KO) mice compared to those from littermate wild-type (WT) mice. RNA samples were extracted from whole livers derived from E18.5 fetuses. Two-condition experiment: Wnt5a KO vs. WT whole livers. Total RNA samples were extracted from E18.5 whole livers. KO and WT samples were a mixture of RNA solutions derived from two Wnt5a KO livers and two WT livers, respectively.
2013-02-07 | E-GEOD-41803 | biostudies-arrayexpress
Project description:Transcriptional profiling of E14 Dlk+ cells derived from Matrix metalloproteinase (MMP)-14 deficient (KO) mice comparing those from littermate wild-type (WT) mice. RNA samples were extrated from FACS-sorted Dlk+CD45-CD71-Ter119- cells derived from E14.5 livers. Transcriptional profiling of postnatal day (P)1 livers derived from MMP-14 deficient (KO) mice comparing those from littermate wild-type (WT) mice. RNA samples were extrated from whole livers derived from P1 mice.
2015-12-25 | GSE73943 | GEO
Project description:Radiation therapy for abdominal tumors is challenging because the small intestine is exquisitely radiosensitive. Unfortunately, there are no FDA-approved therapies to prevent or mitigate GI radiotoxicity. The EGLN protein family are oxygen sensors that regulate cell survival and metabolism through the degradation of hypoxia-inducible factors (HIFs). Our group has previously shown that stabilization of HIF2 through genetic deletion or pharmacologic inhibition of the EGLNs mitigates and protects against GI radiotoxicity in mice by improving intestinal crypt stem cell survival. Here we aimed to elucidate the molecular mechanisms by which HIF2 confers GI radioprotection. We developed duodenal organoids from mice, transiently overexpressed non-degradable HIF2, and performed bulk RNA sequencing. Interestingly, HIF2 upregulated known radiation modulators and genes involved in GI homeostasis, including Wnt5a. Non-canonical Wnt5a signaling has been shown by other groups to improve intestinal crypt regeneration in response to injury. Here we show that HIF2 drives Wnt5a expression in multiple duodenal organoid models. Luciferase reporter assays performed in human cells showed that HIF2 directly activates the WNT5A promoter via a hypoxia response element. We then evaluated crypt regeneration using spheroid formation assays. Duodenal organoids that were pre-treated with recombinant Wnt5a had a higher cryptogenic capacity after irradiation, compared to vehicle-treated organoids. Conversely, we found that Wnt5a knockout decreased the cryptogenic potential of intestinal stem cells following irradiation. Treatment with recombinant Wnt5a prior to irradiation rescued the cryptogenic capacity of Wnt5a knockout organoids, indicating that Wnt5a is necessary and sufficient for duodenal radioprotection. Taken together, our results.txt suggest that HIF2 radioprotects the GI tract by inducing Wnt5a expression.
2021-12-15 | GSE186927 | GEO
Project description:In this study we generated mice with constitutive deletion of microRNA Mir483, which is imprinted and expressed from the paternal allele only. Whole transcriptome analysis was performed by RNA-seq in livers collected from E18.5 fetuses (mutants with deletion of paternal allele - Mir483Pat-KO - and wild-type controls).
2024-02-26 | GSE256302 | GEO
Project description:In this study we generated mice with constitutive deletion of microRNA Mir483, which is imprinted and expressed from the paternal allele only. Global analysis of microRNA expression was performed by miRNA-seq in livers collected from E18.5 fetuses (mutants with deletion of paternal allele - Mir483Pat-KO - and wild-type controls).
2024-02-26 | GSE256305 | GEO
Project description:Wnt5A is released from macrophages during systemic inflammation and sepsis. However, the early response targets for the paracrine action of macrophage derived Wnt5A in vascular endothelial cells still remain unclear. Here we show that Wnt5A regulates the expression of distinct molecular targets involved in inflammation, coagulation and extracellular matrix remodeling. The proteins encoded by these genes are direct targets for known drugs. Regulation of these specific targets by Wnt5A can modulate the drug response and efficiency.
2021-06-09 | GSE145987 | GEO
Project description:Inflammatory Wnt5A signalling in human macrophages was found to be critically involved in severe systemic inflammatory response. However, the targets of Wnt5A in endothelial cells and downstream mechanisms by which Wnt5A might induce endothelial inflammation still remain unclear. We show that Wnt5A principally regulate genes involved endothelial cytoskeleton rearrangements and impairs the barrier function of cultured endothelial monolayer causing hyper permeability. We further prove that Wnt5A neither affects the expression of adhesion molecules nor induces cytokine storm in endothelial cells. These findings suggest that Wnt5A, secreted by activated macrophages during septic inflammation, paracrinically act on the endothelial wall, causing endothelial barrier breakdown and subsequent vascular leakage in sepsis.
2016-10-03 | GSE62281 | GEO
Project description:About half of all melanomas harbor a constitutively active mutant BRAFV600E/K kinase that can be selectively inhibited by targeted BRAF inhibitors (BRAFi). While patients treated with BRAFi initially exhibit measurable clinical improvement, the majority of patients eventually develop drug resistance and relapse. We observe significant elevation of WNT5A in a subset of tumors from patients exhibiting disease progression on BRAFi therapy. WNT5A transcript and protein are also elevated in BRAFi-resistant melanoma cell lines generated by long-term in vitro treatment with BRAFi. RNAi-mediated reduction in levels of endogenous WNT5A in melanoma decreases cell growth, increases apoptosis in response to BRAFi challenge, and decreases the activity of pro-survival AKT signaling. Overexpression of WNT5A conversely promotes melanoma growth and tumorigenesis and activates AKT signaling. Similar to WNT5A knockdown, knockdown of the WNT receptors FZD7 and RYK inhibits growth, sensitizes melanoma cells to BRAFi, and reduces AKT activation. Together, these findings suggest that chronic BRAF inhibition elevates WNT5A expression, which then acts through FZD7 and RYK to promote AKT signaling, leading to increased growth and therapeutic resistance. Increased WNT5A expression in BRAFi-resistant melanomas also correlates with an associated transcriptional signature, which identifies potential therapeutic targets to reduce clinical resistance to BRAFi. Expression of WNT5A-correlated genes was compared in melanoma cell lines generated to be resistant to PLX4032 and the their associated naïve parental line Basal expression of the WNT5A-correlated genes was also measured in experiments comparing each naïve line to a mixed reference pool containing equal amounts of 47 melanoma cell lines.
2014-03-06 | E-GEOD-55583 | biostudies-arrayexpress
Project description:Non-canonical Wnt signaling activated by Wnt5a and Wnt11 is required for the development of second heart field cardiac progenitor cells in mice. However, the pathophysiological role of non-canonical Wnt signaling in the adult heart has not been fully elucidated. Here we show that cardiomyocyte-specific Wnt5a knockout mice exhibit improved systolic function and reduced expression of mechanosensitive genes including Nppb compared to control mice when subjected to pressure overload. In cultured cardiac myocytes, Wnt5a knockdown reduces the upregulation of Nppb gene expression and YAP nuclear translocation induced by cyclic cell stretch. Wnt5a knockdown-induced Nppb downregulation in response to cell stretch is rescued by inhibition of Hippo pathway, and the rescue effect of Hippo inhibition is canceled by YAP knockdown. These results collectively suggest that Wnt5a-YAP signaling axis mediates mechanotransduction in cardiac myocytes and contributes to the transition to heart failure.
2023-07-17 | GSE200666 | GEO
Project description:Non-canonical Wnt signaling activated by Wnt5a and Wnt11 is required for the development of second heart field cardiac progenitor cells in mice. However, the pathophysiological role of non-canonical Wnt signaling in the adult heart has not been fully elucidated. Here we show that cardiomyocyte-specific Wnt5a knockout mice exhibit improved systolic function and reduced expression of mechanosensitive genes including Nppb compared to control mice when subjected to pressure overload. In cultured cardiac myocytes, Wnt5a knockdown reduces the upregulation of Nppb gene expression and YAP nuclear translocation induced by cyclic cell stretch. Wnt5a knockdown-induced Nppb downregulation in response to cell stretch is rescued by inhibition of Hippo pathway, and the rescue effect of Hippo inhibition is canceled by YAP knockdown. These results collectively suggest that Wnt5a-YAP signaling axis mediates mechanotransduction in cardiac myocytes and contributes to the transition to heart failure.
2023-07-17 | GSE200665 | GEO