CRISPR screen for regulators of cadherin based cell to cell adhesion
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1026136 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26327782.fastq.gz | Fastqsanger.gz | |||
| SRR26327783.fastq.gz | Fastqsanger.gz | |||
| SRR26327784.fastq.gz | Fastqsanger.gz | |||
| SRR26327785.fastq.gz | Fastqsanger.gz | |||
| SRR26327786.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:Pooled Crispr based genome wide screen to find potential (transcriptional) regulators and pathways underlying the regulation of cadherin based cell to cell adhesion.
2024-07-03 | GSE244919 | GEO
Project description:Loss of the epithelial adhesion molecule E-cadherin is thought to enable metastasis by disrupting intercellular contacts - an early step in metastatic dissemination. To further investigate the molecular basis of this notion, we use two methods to inhibit E-cadherin function that distinguish between E-cadherin's cell-cell adhesion and intracellular signaling functions. While the disruption of cell-cell contacts alone does not enable metastasis, the loss of E-cadherin protein does, through induction of an epithelial-to-mesenchymal transition, invasiveness and anoikis-resistance. We find the E-cadherin binding partner beta-catenin to be necessary but not sufficient for induction of these phenotypes. In addition, gene expression analysis shows that E-cadherin loss results in the induction of multiple transcription factors, at least one of which, Twist, is necessary for E-cadherin loss-induced metastasis. These findings indicate that E-cadherin loss in tumors contributes to metastatic dissemination by inducing wide-ranging transcriptional and functional changes. Keywords: E-cadherin knockdown, dominant-negative E-cadherin expression, E-cadherin and Beta-catenin double knockdown
2008-01-15 | GSE9691 | GEO
Project description:Loss of the epithelial adhesion molecule E-cadherin is thought to enable metastasis by disrupting intercellular contactsâan early step in metastatic dissemination. To further investigate the molecular basis of this notion, we use two methods to inhibit E-cadherin function that distinguish between E-cadherinâs cell-cell adhesion and intracellular signaling functions. While the disruption of cell-cell contacts alone does not enable metastasis, the loss of E-cadherin protein does, through induction of an epithelial-to-mesenchymal transition, invasiveness and anoikis-resistance. We find the E-cadherin binding partner ï¢-catenin to be necessary but not sufficient for induction of these phenotypes. In addition, gene expression analysis shows that E-cadherin loss results in the induction of multiple transcription factors, at least one of which, Twist, is necessary for E-cadherin loss-induced metastasis. These findings indicate that E-cadherin loss in tumors contributes to metastatic dissemination by inducing wide-ranging transcriptional and functional changes. Experiment Overall Design: Gene expression changes induced by knockdown of E-cadherin, expression of dominant-negative E-cadherin and double knockdown of E-cadherin and Beta-catenin in immortalized human mammary epithelial cells Experiment Overall Design: Four groups, three biological replicates per group. shCntrl expressing cells are the control group
2008-11-06 | E-GEOD-9691 | biostudies-arrayexpress
Project description:CRISPR screen for NMD regulators
| PRJNA602918 | ENA
Project description:The aggregation of nephron progenitor cells (NPC) is required to form the nephron precursor renal vesicle (RV) as they undergo the mesenchymal-to-epithelial transition (MET). Canonical Wnt signaling regulates the MET of NPCs via the effector molecule β-catenin. β-catenin acts as a transcriptional co-activator during the differentiation of NPCs, however, if it has any role as an adhesion regulating molecule via the cadherin-catenin complex is currently unknown. Using in vitro NPC culture system with gene editing and modulated Wnt signaling input, we investigated the morphological transition of NPCs and its underlying mechanism modeling the initial step of the MET in vivo. Increasing Wnt signaling input with the small molecule agonist CHIR resulted in the aggregation of NPCs similar to the generation of the nephron anlagen. By removing β- and α-catenin from the NPCs, NPCs are sorted out from these aggregates, demonstrating the key role of the cadherin-catenin complex in the aggregation. β-catenin was essential for the induction, however, the removal of α-catenin did not affect the transcriptional profile of NPCs. Removal of extracellular Ca2+ resulted in the transient loss of cell-cell contacts suggesting the role of cadherins in the aggregation process. The analysis of in vitro bulk RNA-seq cadherin expression profile matched the in vivo cadherin expression profile determined by single-cell RNA-seq. The combined removal of pre-existing and inducible cadherins phenocopied the results of β- and α-catenin KO experiments highlighting the crucial role of the cadherin-catenin complex by multiple lines of evidence. Notably, the induction of NPCs is independent of their aggregation. The in vitro modeling of nephron development provides a mechanistic understanding how cell adhesion is regulated via the cadherin-catenin complex during nephrogenesis.
2024-07-29 | GSE232606 | GEO
Project description:The maturation of dendritic cells (DCs) after exposure to microbial products or inflammatory mediators plays a critical role in initiating the immune response. We found that maturation can also occur under steady state conditions, triggered by alterations in E-cadherin-mediated DC-DC adhesion. Selective disruption of these interactions induced the typical features of DC maturation including the upregulation of costimulatory molecules, MHC class II, and chemokine receptors. These events were triggered at least in part by activation of the b-catenin pathway. However, unlike maturation induced by microbial products, E-cadherin-stimulated DCs failed to release immunostimulatory cytokines, exhibiting an entirely different transcriptional profile. As a result, E-cadherin-stimulated DCs elicited an entirely different T cell response in vivo, generating T cells with a regulatory as opposed to an effector phenotype. These DCs induced tolerance in vivo and may thus contribute to the elusive steady state “tolerogenic DCs”. Keywords: time-course, dendritic cell maturation
2007-10-06 | GSE9241 | GEO
Project description:The maturation of dendritic cells (DCs) after exposure to microbial products or inflammatory mediators plays a critical role in initiating the immune response. We found that maturation can also occur under steady state conditions, triggered by alterations in E-cadherin-mediated DC-DC adhesion. Selective disruption of these interactions induced the typical features of DC maturation including the upregulation of costimulatory molecules, MHC class II, and chemokine receptors. These events were triggered at least in part by activation of the b-catenin pathway. However, unlike maturation induced by microbial products, E-cadherin-stimulated DCs failed to release immunostimulatory cytokines, exhibiting an entirely different transcriptional profile. As a result, E-cadherin-stimulated DCs elicited an entirely different T cell response in vivo, generating T cells with a regulatory as opposed to an effector phenotype. These DCs induced tolerance in vivo and may thus contribute to the elusive steady state âtolerogenic DCsâ. Experiment Overall Design: We performed a genome-wide microarray analysis to study the expression profiles of DCs matured by CD as opposed to a conventional TLR agonist (E. coli, which stimulates multiple TLRs). RNA was isolated from human CD34+ DCs at various times after stimulation and used to probe Affymetrix U95Av2 chips. A time course was followed after various stimuli, with single chips used per time point. >700 genes were found differentially regulated upon maturation by either CD or bacterial stimulation. Cluster analysis revealed that after an early phase (1-3 hr) of similarity, expression profiles exhibited by the two sets of DCs diverged dramatically at later time points (>6 hr). A number of transcripts were markedly upregulated in the bacteria-stimulated set that remained relatively unchanged or actually decreased in the cluster-disrupted set. There were some transcripts upregulated in cluster-disrupted cells, however, with at least some of these increases prevented by adding anti-E-cadherin mAb under conditions that blocked maturation. Clearly, the transcriptional events induced by alteration of E-cadherin-mediated adhesion were quite distinct from those induced by TLR activation.
2008-06-16 | E-GEOD-9241 | biostudies-arrayexpress
Project description:E-cadherin-mediated cell-cell adhesion and signaling plays an essential role in development and maintenance of healthy epithelial tissues. Adhesiveness mediated by E-cadherin is conferred by its extracellular cadherin domains and is regulated by an assembly of adaptors and enzymes associated with its cytoplasmic tail. Here, we used proximity biotinylation and quantitative proteomics to identify 561 proteins in the vicinity of E-cadherin’s cytoplasmic tail. Isolation of E-cadherin-mediated adhesion plaques from a cell-glass interface added positional context to the proteomic results. Moreover, using expression of GFP-tagged fusion proteins, we determine the subcellular localization of 83 of the E-cadherin proximal proteins, and identify 24 novel adherens junction components. We employed a structure-informed database of protein-protein interactions to construct a comprehensive E-cadherin interactome, containing 82 known and 419 previously uncharacterized proteins. Finally, we found that calcium chelation did not disrupt most protein interactions with E-cadherin, suggesting that most E-cadherin interactions are independent of cell-cell adhesion.
2016-07-06 | PXD000448 | Pride
Project description:Single-cell activation screen identifies hepatic maturation regulators with zonal resolution
| PRJNA1015558 | ENA
Project description:Identify proinsulin regulators using CRISPR screen and mouse genetics [CRISPR screen]
| PRJNA1030057 | ENA