Single cell level characterization of Cdh11 deficiency-induced changes in pancreatic cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA978564 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR24796081.fastq.gz | Fastqsanger.gz | |||
| SRR24796083.fastq.gz | Fastqsanger.gz | |||
| SRR24796084.fastq.gz | Fastqsanger.gz | |||
| SRR24796085.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 5 |
Similar Datasets
Project description:Cadherin 11 (Cdh11), a cell-to-cell adhesion molecule, has been suggested to promote tumor growth and immunosuppression in PDAC, and Cdh11 inhibition significantly extended survival in mice with PDAC. However, the mechanisms by which Cdh11 deficiency influences PDAC progression and anti-tumor immune responses has yet to be fully elucidated. To investigate Cdh11-deficiency induced changes in PDAC tumor microenvironment (TME), we crossed p48-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+ (KPC) mice with Cdh11+/- mice and performed single-cell RNA sequencing (scRNA-seq) of the non-immune (CD45-) and immune (CD45+) compartment of KPC tumor bearing Cdh11 proficient (KPC-Cdh11+/+) and Cdh11 deficient (KPC-Cdh11+/-) mice.
2025-05-01 | GSE233915 | GEO
Project description:Cadherin 11 (Cdh11) is a member of the cadherin superfamily, a group of transmembrane proteins that are principally located in adheren junctions and mediate cell-to-cell adhesion. Dysregulation of Cdh11 in fibroblast populations has been associated with pathologic processes such as inflammation, fibrosis, and cancer. We sought to characterise Cdh11+/- lung fibroblast populations using an inducible Cdh11 reporter mouse model.
2026-05-05 | GSE324380 | GEO
Project description:Background & Aims: Pancreatic ductal adenocarcinomas (PDAC) are characterized by fibrosis and an abundance of cancer-associated fibroblasts (CAFs). We investigated strategies to disrupt interactions among CAFs, the immune system, and cancer cells, focusing on adhesion molecule cadherin 11 (CDH11), which has been associated with other fibrotic disorders and is expressed by activated fibroblasts. Methods: We compared levels of CDH11 mRNA in human pancreatitis and pancreatic cancer tissues and cells, compared with normal pancreas, and measured levels of CDH11 protein in human and mouse pancreatic lesions and normal tissues. We crossed p48-Cre;LSL-KrasG12D/+;LSL-Trp53R172H/+ (KPC) mice with CDH11-knockout mice and measured survival times of offspring. Pancreata were collected and analyzed by histology, immunohistochemistry, and (single-cell) RNA sequencing; RNA and proteins were identified by imaging mass cytometry. Some mice were given injections of PD1 antibody or gemcitabine and survival was monitored. Pancreatic cancer cells from KPC mice were subcutaneously injected into Cdh11+/+ and Cdh11–/– mice and tumor growth was monitored. Pancreatic cancer cells (mT3) from KPC mice (C57BL/6), were subcutaneously injected into Cdh11+/+ (C57BL/6J) mice and mice were given injections of antibody against CDH11, gemcitabine, or small molecule inhibitor of CDH11 (SD133) and tumor growth was monitored. Results: Levels of CDH11 mRNA and protein were significantly higher in CAFs than in pancreatic cancer epithelial cells, human or mouse pancreatic cancer cell lines, or immune cells. KPC/Cdh11+/– and KPC/Cdh11–/– mice survived significantly longer than KPC/Cdh11+/+ mice. Markers of stromal activation entirely surrounded pancreatic intraepithelial neoplasias in KPC/Cdh11+/+ mice and incompletely in KPC/Cdh11+/– and KPC/Cdh11–/– mice, whose lesions also contained fewer FOXP3+ cells in the tumor center. Compared with pancreatic tumors in KPC/Cdh11+/+ mice, tumors of KPC/Cdh1+/– mice had increased markers of antigen processing and presentation; more lymphocytes and cytokines associated with lymphocyte infiltration; decreased extracellular matrix components; and reductions in markers and cytokines associated with immunosuppression. Administration of the PD1 antibody did not prolong survival of KPC mice with 0, 1, or 2 alleles of Cdh11. Gemcitabine extended survival only of KPC/Cdh11+/– and KPC/Cdh11–/– mice or reduced subcutaneous tumor growth in mT3 engrafted Cdh11+/+ mice given in combination with the CDH11 antibody. A small molecule inhibitor of CDH11 reduced growth of pre-established mT3 subcutaneous tumors only if T and B cells were present in mice. Conclusions: Knockout or inhibition of CDH11, which is expressed by CAFs in the pancreatic tumor stroma, reduces growth of pancreatic tumors, increases their response to gemcitabine, and significantly extends survival of mice. CDH11 promotes immunosuppression and extracellular matrix deposition, and might be developed as a therapeutic target for pancreatic cancer.
2020-12-01 | GSE157781 | GEO
Project description:The molecular etiology of numerous risk genes for autism spectrum disorder (ASD), including CDH11, remains elusive. We investigated the role of CDH11 in the development of ASD-related behaviors using gene-deficient mice. CDH11 is enriched at synapses in glutamatergic neurons of the anterior cingulate cortex (ACC), which project to the striatum, nucleus accumbens, and amygdala. Ablation of Cdh11 in these neurons during development increases self-grooming and reduces sociability, with decreased neuronal activity in the ACC. Chemogenetic inhibition of ACC glutamatergic neurons recapitulates the over-grooming phenotype, while activation of these neurons mitigates self-grooming in Cdh11-deficient mice. Proteomics of ACC synaptosomes and CDH11 interactomes suggest the involvement of CDH11 in synaptic vesicle trafficking, supported by reduced presynaptic vesicle density at excitatory synapses in Cdh11-deficient mice. These findings highlight the critical role of CDH11 in ASD-related brain circuit development and offer insights into the molecular mechanisms and potential therapeutic targets for ASD.
2025-08-08 | PXD055834 | Pride
Project description:The molecular etiology of numerous risk genes for autism spectrum disorder (ASD), including CDH11, remains elusive. We investigated the role of CDH11 in the development of ASD-related behaviors using gene-deficient mice. CDH11 is enriched at synapses in glutamatergic neurons of the anterior cingulate cortex (ACC), which project to the striatum, nucleus accumbens, and amygdala. Ablation of Cdh11 in these neurons during development increases self-grooming and reduces sociability, with decreased neuronal activity in the ACC. Chemogenetic inhibition of ACC glutamatergic neurons recapitulates the over-grooming phenotype, while activation of these neurons mitigates self-grooming in Cdh11-deficient mice. Proteomics of ACC synaptosomes and CDH11 interactomes suggest the involvement of CDH11 in synaptic vesicle trafficking, supported by reduced presynaptic vesicle density at excitatory synapses in Cdh11-deficient mice. These findings highlight the critical role of CDH11 in ASD-related brain circuit development and offer insights into the molecular mechanisms and potential therapeutic targets for ASD
2025-08-08 | PXD056411 | Pride
Project description:The molecular etiology of numerous risk genes for autism spectrum disorder (ASD), including CDH11, remains elusive. We investigated the role of CDH11 in the development of ASD-related behaviors using gene-deficient mice. CDH11 is enriched at synapses in glutamatergic neurons of the anterior cingulate cortex (ACC), which project to the striatum, nucleus accumbens, and amygdala. Ablation of Cdh11 in these neurons during development increases self-grooming and reduces sociability, with decreased neuronal activity in the ACC. Chemogenetic inhibition of ACC glutamatergic neurons recapitulates the over-grooming phenotype, while activation of these neurons mitigates self-grooming in Cdh11-deficient mice. Proteomics of ACC synaptosomes and CDH11 interactomes suggest the involvement of CDH11 in synaptic vesicle trafficking, supported by reduced presynaptic vesicle density at excitatory synapses in Cdh11-deficient mice. These findings highlight the critical role of CDH11 in ASD-related brain circuit development and offer insights into the molecular mechanisms and potential therapeutic targets for ASD.
2025-08-08 | PXD056074 | Pride
Project description:Patients with advanced bladder cancer (BC) have a poor prognosis and limited treatment options. Therefore, we searched for potential new therapeutic targets using existing big data. First, we collected gene expression datasets of BC cell lines from the Gene Expression Omnibus (GEO) and extracted genes that were highly expressed in advanced BC cell lines. We also extracted genes highly expressed in advanced BC patients from The Cancer Genome Atlas (TCGA). We performed an integrated analysis of these genes to identify genes involved in BC progression, combined with Kaplan-Meier analysis, and identified CDH11 as an involved gene in bladder cancer progression. CDH11 knockdown (KD) cells were established using shRNA against UM-UC-3, an advanced BC cell line. While CDH11 KD did not alter cell proliferation, invasion nor migration in vitro, CDH11 KD significantly suppressed tumor growth in in vivo subcutaneous xenograft mice model. RNA-seq revealed that CDH11 KD cells decreased the expression of genes related to mitochondrial metabolism, and in fact, a flux analyzer revealed decreased mitochondrial activity in the KD cell line. Furthermore, the experiments using CDH11 inhibitor also showed a decrease in mitochondrial activity in vitro, and inhibition of tumor growth in vivo as well as knockdown experiments. These results suggest that CDH11 is involved in BC progression and is a potential therapeutic target.
2025-12-04 | GSE277038 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant accumulation of collagen-secreting myofibroblasts. Development of effective therapies is limited due to incomplete understanding of molecular mechanisms regulating myofibroblast expansion. FOXF1 transcription factor is expressed in resident lung fibroblasts, but its role in lung fibrosis remains unknown due to the lack of genetic mouse models. Through comprehensive analysis of human IPF genomics data, lung biopsies and transgenic mice with fibroblast-specific inactivation of FOXF1, the present study shows that FOXF1 inhibits pulmonary fibrosis. FOXF1 deletion increases myofibroblast invasion, collagen secretion, and promotes a switch from of N-cadherin (CDH2) to Cadherin-11 (CDH11), which is critical step in acquisition of pro-fibrotic phenotype. FOXF1 directly binds to Cdh2 and Cdh11 promoters and differentially regulates transcription of these genes. Re-expression of CDH2 or inhibition of CDH11 in FOXF1-deficient cells reduces myofibroblast invasion in vitro. FOXF1 inhibits pulmonary fibrosis by regulating a switch from CDH2 to CDH11 in lung myofibroblasts.
2018-08-09 | GSE110408 | GEO
Project description:Lung metastasis is a major cause of death in patients with esophageal squamous cell carcinoma (ESCC) and its tumor microenvironment (TME) is highly complex; however, the molecular mechanisms of ESCC lung metastasis are unclear. In this study, the first comprehensive single-cell atlas of ESCC lung metastasis is established using single-cell RNA sequencing of 11 patient samples. The findings highlight the dynamic evolutionary patterns of the TME and distinct characteristics of key cellular subpopulations. The immune microenvironment exhibited significant alterations, with a subpopulation of pro-carcinogenic cancer-associated fibroblasts (CAFs) in primary ESCC foci and lung metastases. Notably, calreticulin CDH11 is exclusively expressed in these CAFs and upregulated in conjunction with lung metastasis of ESCC. CDH11 modulates the AKT-related signaling pathway through its interaction with FGFR1, influencing CAF-mediated extracellular matrix remodeling, thereby facilitating metastatic progression. Application of the CDH11 inhibitor, celecoxib, presents a promising new strategy for targeting lung metastasis in ESCC. The molecular mechanisms underlying the lung metastatic microenvironment of ESCC, which are expected to improve the molecular typing accuracy of ESCC lung metastasis to the single-cell level contribute to the development of a precision therapeutic system based on the modulation of the stromal microenvironment, with significant clinical translational potential.
2025-09-29 | GSE309393 | GEO
Project description:Lung metastasis is a major cause of death in patients with esophageal squamous cell carcinoma (ESCC) and its tumor microenvironment (TME) is highly complex; however, the molecular mechanisms of ESCC lung metastasis are unclear. In this study, the first comprehensive single-cell atlas of ESCC lung metastasis is established using single-cell RNA sequencing of 11 patient samples. The findings highlight the dynamic evolutionary patterns of the TME and distinct characteristics of key cellular subpopulations. The immune microenvironment exhibited significant alterations, with a subpopulation of pro-carcinogenic cancer-associated fibroblasts (CAFs) in primary ESCC foci and lung metastases. Notably, calreticulin CDH11 is exclusively expressed in these CAFs and upregulated in conjunction with lung metastasis of ESCC. CDH11 modulates the AKT-related signaling pathway through its interaction with FGFR1, influencing CAF-mediated extracellular matrix remodeling, thereby facilitating metastatic progression. Application of the CDH11 inhibitor, celecoxib, presents a promising new strategy for targeting lung metastasis in ESCC. The molecular mechanisms underlying the lung metastatic microenvironment of ESCC, which are expected to improve the molecular typing accuracy of ESCC lung metastasis to the single-cell level contribute to the development of a precision therapeutic system based on the modulation of the stromal microenvironment, with significant clinical translational potential.
2025-09-29 | GSE309392 | GEO