Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA287701 | ENA |
REPOSITORIES: ENA
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Project description:Wnt/b-catenin signaling regulates sequential fate decisions of murine cortical precursor cells
| PRJNA287701 | ENA
Project description:Wnt/β-catenin signaling regulates progenitor cell fate decisions during lung development and in various adult tissues. Ectopic activation of Wnt/β-catenin signaling promotes tissue repair in emphysema, a devastating lung disease with progressive loss of parenchymal lung tissue. The identity of Wnt/β-catenin responsive progenitor cells and the potential impact of Wnt/β-catenin signaling on adult distal lung epithelial progenitor cell function in emphysema, are poorly understood. Here, we used a TCF/Lef:H2B/GFP reporter mice to investigate the role of Wnt/β-catenin signaling in lung organoid formation. We identified an organoid-forming adult distal lung epithelial progenitor cell population characterized by a low Wnt/β-catenin activity, which was enriched in club and alveolar epithelial type (AT)II cells. To further characterize the lung epithelial populations with different Wnt activities, we perform microarray analysis using freshly isolated Wnthigh/low/negative lung epithelial cells to study their transcriptome, specially the enriched genes and signaling pathways in the Wnt low population related epithelial stem cell functions.
2020-06-12 | GSE150957 | GEO
Project description:Background Wnt signaling is implicated in many developmental decisions, including stem cell control, as well as in cancer. There are relatively few target genes known of the Wnt pathway. Results We have identified target genes of Wnt signaling using microarray technology and human embryonal carcinoma cells stimulated with active Wnt protein. The ~50 genes upregulated early after Wnt addition include the previously known Wnt targets Cyclin D1, MYC, ID2 and beta TRCP. The newly identified targets, which include MSX1, MSX2, Nucleophosmin, Follistatin, TLE/Groucho, Ubc4/5E2, CBP/P300, Frizzled and REST/NRSF, have important implications for understanding the roles of Wnts in development and cancer. The protein synthesis inhibitor cycloheximide blocks induction by Wnt, consistent with a requirement for newly synthesized beta - catenin protein prior to target gene activation. The promoters of nearly all the target genes we identified have putative TCF binding sites; and we show that the TCF binding site is required for induction of Follistatin. Several of the target genes have a cooperative response to a combination of Wnt and BMP. Conclusion Wnt signaling activates genes that promote stem cell fate and inhibit cellular differentiation; and regulates a remarkable number of genes involved in its own signaling system.
2005-09-02 | E-SMDB-1827 | biostudies-arrayexpress
Project description:Background Wnt signaling is implicated in many developmental decisions, including stem cell control, as well as in cancer. There are relatively few target genes known of the Wnt pathway. Results We have identified target genes of Wnt signaling using microarray technology and human embryonal carcinoma cells stimulated with active Wnt protein. The ~50 genes upregulated early after Wnt addition include the previously known Wnt targets Cyclin D1, MYC, ID2 and beta TRCP. The newly identified targets, which include MSX1, MSX2, Nucleophosmin, Follistatin, TLE/Groucho, Ubc4/5E2, CBP/P300, Frizzled and REST/NRSF, have important implications for understanding the roles of Wnts in development and cancer. The protein synthesis inhibitor cycloheximide blocks induction by Wnt, consistent with a requirement for newly synthesized beta - catenin protein prior to target gene activation. The promoters of nearly all the target genes we identified have putative TCF binding sites; and we show that the TCF binding site is required for induction of Follistatin. Several of the target genes have a cooperative response to a combination of Wnt and BMP. Conclusion Wnt signaling activates genes that promote stem cell fate and inhibit cellular differentiation; and regulates a remarkable number of genes involved in its own signaling system. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set Using regression correlation
2005-09-08 | E-GEOD-3262 | biostudies-arrayexpress
Project description:Canonical Wnt and Nodal signaling are both required for induction of the primitive streak (PS), which guides organization of the early embryo. The Wnt effector β-catenin is thought to function in these early lineage specification decisions via transcriptional activation of Nodal signaling. Here, we demonstrate a broader role for β-catenin in PS formation by analyzing its genome-wide binding in a human embryonic stem cell model of PS induction. β-catenin occupies regulatory regions in numerous PS and neural crest genes, and direct interactions between β-catenin and the Nodal effectors SMAD2/3 are required at these regions for PS gene activation. Furthermore, OCT4 binding in proximity to these sites is likewise required for PS induction, suggesting a collaborative interaction between β-catenin and OCT4. Induction of neural crest genes by β-catenin is repressed by SMAD2/3, ensuring proper lineage specification. This study provides mechanistic insight into how Wnt signaling controls early cell lineage decisions. Examination of β-catenin binding in hESC incubated in media control (RPMI), media containing CHIR or CHIR+SB for 6h and analyzed by ChIP-sequencing
2015-03-31 | E-GEOD-58476 | biostudies-arrayexpress
Project description:The Wnt/alpha-catenin pathway plays a central role in epidermal homeostasis and regeneration but how it affects fibroblast fate decisions is unknown. Here, we investigated the effect of targeted alpha-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of Sca1- and Sca1+ neonatal fibroblasts, from upper and lower dermis respectively, confirmed that Sca1+ cells had a pre-adipocyte signature and revealed differential expression of Wnt/alpha‐catenin-associated genes. By targeting all fibroblasts or selectively targeting Dlk1+ lower dermal fibroblasts, we found that -catenin stabilization between E16.5 and P2 resulted in a reduction in the dermal adipocyte layer with a corresponding increase in dermal fibrosis and an altered hair cycle. The fibrotic phenotype correlated with a reduction in the potential of Sca1+ fibroblasts to undergo adipogenic differentiation ex vivo. Our findings indicate that Wnt/alpha-catenin signaling controls adipogenic cell fate within the lower dermis, which potentially contributes to the pathogenesis of fibrotic skin diseases.
2016-01-12 | GSE76751 | GEO
Project description:The evolutionarily conserved Wnt/?-catenin signaling pathway plays a fundamental role during metazoan development, regulating numerous processes including cell fate specification, cell migration, and stem cell renewal. Wnt ligand binding leads to stabilization of the transcriptional effector ?-catenin and upregulation of target gene expression to mediate a cellular response. During larval development of the nematode Caenorhabditis elegans, Wnt/?-catenin pathways act in fate specification of two hypodermal cell types, the ventral vulval precursor cells (VPCs) and the lateral seam cells. Because little is known about targets of the Wnt signaling pathways acting during larval VPC and seam cell differentiation, we sought to identify genes regulated by Wnt signaling in these two hypodermal cell types. We conditionally activated Wnt signaling in larval animals and performed cell type?specific "mRNA tagging" to enrich for VPC and seam cell?specific mRNAs, and then used microarray analysis to examine gene expression compared to control animals. Two hundred thirty-nine genes activated in response to Wnt signaling were identified, and we characterized 50 genes further. The majority of these genes are expressed in seam and/or vulval lineages during normal development, and reduction of function for nine genes caused defects in the proper division, fate specification, fate execution, or differentiation of seam cells and vulval cells. Therefore, the combination of these techniques was successful at identifying potential cell type?specific Wnt pathway target genes from a small number of cells and at increasing our knowledge of the specification and behavior of these C. elegans larval hypodermal cells.
2015-11-18 | GSE52747 | GEO
Project description:Canonical Wnt and Nodal signaling are both required for induction of the primitive streak (PS), which guides organization of the early embryo. The Wnt effector β-catenin is thought to function in these early lineage specification decisions via transcriptional activation of Nodal signaling. Here, we demonstrate a broader role for β-catenin in PS formation by analyzing its genome-wide binding in a human embryonic stem cell model of PS induction. β-catenin occupies regulatory regions in numerous PS and neural crest genes, and direct interactions between β-catenin and the Nodal effectors SMAD2/3 are required at these regions for PS gene activation. Furthermore, OCT4 binding in proximity to these sites is likewise required for PS induction, suggesting a collaborative interaction between β-catenin and OCT4. Induction of neural crest genes by β-catenin is repressed by SMAD2/3, ensuring proper lineage specification. This study provides mechanistic insight into how Wnt signaling controls early cell lineage decisions.
2015-03-31 | GSE58476 | GEO
Project description:The Wnt/alpha-catenin pathway plays a central role in epidermal homeostasis and regeneration but how it affects fibroblast fate decisions is unknown. Here, we investigated the effect of targeted alpha-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of Sca1- and Sca1+ neonatal fibroblasts, from upper and lower dermis respectively, confirmed that Sca1+ cells had a pre-adipocyte signature and revealed differential expression of Wnt/alphaâ??catenin-associated genes. By targeting all fibroblasts or selectively targeting Dlk1+ lower dermal fibroblasts, we found that ï?¢-catenin stabilization between E16.5 and P2 resulted in a reduction in the dermal adipocyte layer with a corresponding increase in dermal fibrosis and an altered hair cycle. The fibrotic phenotype correlated with a reduction in the potential of Sca1+ fibroblasts to undergo adipogenic differentiation ex vivo. Our findings indicate that Wnt/alpha-catenin signaling controls adipogenic cell fate within the lower dermis, which potentially contributes to the pathogenesis of fibrotic skin diseases. The dermis was separated from back skin of PDGFRAeGFP postnatal pups (P2) by incubation with thermolysin (0.25 mg/ml) (Sigma T7902) overnight at 4° and further processed as previously described (Collins et al., 2011). Cells were labeled in PBS + 10% FBS TruStain fcX anti-mouse blocking buffer with the following antibodies: anti-mouse Ly-6A/E (Sca-1)-Alexa Fluor-700 17. Two populations of cells were collected in triplicate. The PDGFRaH2BeGFP/Sca1- and the PDGFRaH2BeGFP/Sca1+. RNA was isolated and prepared for microarray analysis and hybridized to Affymetrix MG430.2A arrays. C, digested in DMEM + 10% FBS containing 2.5 mg/mL collagenase I (Gibco 17100- 017), and further processed
2016-01-12 | E-GEOD-76751 | biostudies-arrayexpress
Project description:Canonical Wnt signaling plays critical roles in development and tissue renewal by regulating β-catenin target genes. Recent evidence showed that β-catenin-independent Wnt signaling is also required for faithful execution of mitosis. This mitotic Wnt signaling functions through Wnt-dependent stabilization of proteins (Wnt/STOP), as well as through components of the LRP6 signalosome. However, the targets and specific functions of mitotic Wnt signaling still remain uncharacterized. Using phosphoproteomics, we identified that Wnt signaling regulates the microtubule depolymerase KIF2A during mitosis. We found that Dishevelled recruits KIF2A via its N-terminal and motor domains, which is further promoted upon LRP6 signalosome formation during mitosis. We show that Wnt signaling modulates KIF2A interaction with PLK1, which is critical for KIF2A localization and the assembly of a bipolar mitotic spindle. Accordingly, Wnt signaling promotes chromosome congression during metaphase by monitoring KIF2A protein levels at the spindle poles both in somatic cells and in pluripotent stem cells. Our findings highlight a novel function of Wnt signaling during cell division, which could have important implications for genome maintenance, notably in stem cells.
2021-11-17 | PXD022724 | Pride