Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA126809 | ENA |
REPOSITORIES: ENA
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Project description:Rationale: The Id1 and Id3 genes play major roles during cardiac development, despite their expression being confined to non-myocardial layers (endocardium – endothelium - epicardium). We previously described that Id1–/–Id3–/– double knockout (dKO) mouse embryos die at mid-gestation from multiple cardiac defects, but early demise precluded the studies of the roles of Id in the adult mice. Objective: To elucidate postnatal roles of Id genes in the heart. Methods and Results: We ablated Id1 gene in the vasculature and Id3 gene globally to generate Tie2Cre+Id1F/–Id3–/– and Tie2Cre+Id1F/FId3–/– conditional KO (Id cKO) embryos. Half of the Id cKO mice die at birth. Postnatal demise was associated with cardiac underdevelopment, enlargement, muscular ventricular septal and endothelial defects. Surviving Id cKO mice exhibited dilated, fibrotic cardiomyopathy associated with defects in the vasculature. The adult cardiac phenotype progressed into heart failure and resembled endomyocardial fibroelastosis. An abnormal vascular response was also observed in the healing process of excisional skin wounds of Id cKO mice. Expression patterns of vascular, fibrotic and hypertrophic markers were altered in the Id cKO hearts, but addition of Insulin-Like Growth Factor binding protein-3 (IGFbp3) reversed gene expression profiles of vascular and fibrotic, but not hypertrophic markers. Conclusions: Conditional ablation of Id genes in the vasculature leads to dilated fibrotic cardiomyopathy. The findings could reveal important insights into the role(s) of the endocardial network of the endothelial lineage to the development of dilated fibrotic cardiomyopathy and identify a potential therapeutic target, IGFbp3, in its treatment.
2010-10-07 | GSE21924 | GEO
Project description:Rationale: The Id1 and Id3 genes play major roles during cardiac development, despite their expression being confined to non-myocardial layers (endocardium â?? endothelium - epicardium). We previously described that Id1â??/â??Id3â??/â?? double knockout (dKO) mouse embryos die at mid-gestation from multiple cardiac defects, but early demise precluded the studies of the roles of Id in the adult mice. Objective: To elucidate postnatal roles of Id genes in the heart. Methods and Results: We ablated Id1 gene in the vasculature and Id3 gene globally to generate Tie2Cre+Id1F/â??Id3â??/â?? and Tie2Cre+Id1F/FId3â??/â?? conditional KO (Id cKO) embryos. Half of the Id cKO mice die at birth. Postnatal demise was associated with cardiac underdevelopment, enlargement, muscular ventricular septal and endothelial defects. Surviving Id cKO mice exhibited dilated, fibrotic cardiomyopathy associated with defects in the vasculature. The adult cardiac phenotype progressed into heart failure and resembled endomyocardial fibroelastosis. An abnormal vascular response was also observed in the healing process of excisional skin wounds of Id cKO mice. Expression patterns of vascular, fibrotic and hypertrophic markers were altered in the Id cKO hearts, but addition of Insulin-Like Growth Factor binding protein-3 (IGFbp3) reversed gene expression profiles of vascular and fibrotic, but not hypertrophic markers. Conclusions: Conditional ablation of Id genes in the vasculature leads to dilated fibrotic cardiomyopathy. The findings could reveal important insights into the role(s) of the endocardial network of the endothelial lineage to the development of dilated fibrotic cardiomyopathy and identify a potential therapeutic target, IGFbp3, in its treatment. Total RNA from heart tissue was isolated (RNeasy, QIAGEN) from P180 WT, Id control, Id cKO, IGFbp3 incubated Id cKO, and control incubated Id cKO. RNA was converted to cDNA, cRNA, and hybridized to DNA sequences contained in the GeneChip Mouse Gene 1.0 ST Array (Affymetrix). Information from at least duplicate samples was compared and filtered by fold change >2 (Id cKO vs WT, Id control vs WT, IGFbp3 incubated Id cKO vs. control incubated Id cKO) and statistical p-value<0.001.
2010-10-07 | E-GEOD-21924 | biostudies-arrayexpress
Project description:TCF3 belongs to E protein family and has the function of transcription factor. TCF3 can directly interact with HLH family proteins ID1 and ID3 to play biological functions. ID1 and ID3 do not have the ability to directly bind to DNA and need to be regulated by TCF3. We found changes in pluripotency in ID1 and ID3 double knockout lines of human ESC, so we suspected that ID1 / 3 played a regulatory role through TCF3. Therefore, TCF3 ChIP-seq was done in WT and KO lines, hoping to find the downstream genes regulated by ID1 / 3 through TCF3, and then regulate hESC pluripotency through these genes.
2022-06-27 | GSE183518 | GEO
Project description:The experiment was designed to achieve Cre recombinase mediated deletion of Id1, Id2 and Id3 in a temporally controlled fashion in tumor cells of Id1, Id2, Id3 floxed mice with the aim of comparing the gene expression profiles of Id expressing versus Id deleted tumors.
2013-04-30 | E-MTAB-1303 | biostudies-arrayexpress
Project description:The diagnosis of B-Cell acute lymphoblastic leukemia (B-ALL) in adults often carries a poor prognosis. ID1 and ID3 genes have been identified as predictors of poor response in Colombian adult B-ALL patients, playing roles in cancer development. In different cancer models, these genes have been associated with immune regulator populations within the tumor immune microenvironment (TIME). B-ALL development alters the immune cell composition and the bone marrow (BM) tumor microenvironment, affecting disease progression and response to therapy. This study analyzes gene expression levels of ID1 and ID3 in relation to TIME and immune evasion. This exploratory study analyzed BM samples from 10 B-ALL adult patients diagnosed at the National Cancer Institute of Colombia. First, RT-qPCR was used to assess ID1 and ID3 expression in BM tumor cells. Flow cytometry characterized immune populations in the TIME. RNA-seq evaluated immune genes associated with B-ALL immune response, while xCell and cytosig analyzed TIME cell profiles and cytokines. Pathway analysis, gene ontology, and differential gene expression (DEGs) were examined, with functional enrichment analysis performed using KEGG ontology. Patients were divided into two groups based on ID1 and ID3 expression, namely basal and overexpression. A total of 94 differentially expressed genes were identified between these groups, with top overexpressed genes associated with neutrophil pathways. Gene set enrichment analysis revealed increased expression of genes associated with neutrophil degranulation, immune response-related neutrophil activation, and neutrophil-mediated immunity. These findings correlated with xCell data. Overexpression group showed significant differences in neutrophils (p=0.0008), monocytes (<0.0001) and CD4+ naive T cells (p=0.0240) compared to basal group patients. Microenvironment and immune scores were also significantly different (p=0.0016 and p=0.0017, respectively), consistent with the flow cytometry results. Elevated cytokine levels associated with neutrophil activation supported these findings. Validation was performed using the TARGET and MILE B-ALL cohorts. Our results show important differences between the expression level of ID1 and ID3 in cancer cells and the populations of TIME, suggesting a role in evading the immune response of ID1 and ID3 in B-ALL, mainly related to neutrophil pathways.
2024-11-08 | GSE276392 | GEO
Project description:Id proteins are dominant negative regulators within the HLH family of proteins. In embryonic stem cells (ESCs), Id1 and Id3 maintain the pluripotent state by preventing neural differentiation. The Id1-interacting protein Zrf1 plays a crucial role as a chromatin-bound factor in specification of the neural fate from ESCs. Here, we show that Id1 blocks Zrf1 recruitment to chromatin, thus preventing the activation of neural genes during ESC differentiation. Moreover, genetic deletion of Id1 in ESCs caused misexpression of more than 6000 genes. Interestingly, the expression of almost half of those genes was restored upon further depletion of Zrf1. We therefore identified Zrf1 as a transcriptional regulator downstream of Id1 in ESCs.
2014-11-05 | GSE58627 | GEO
Project description:Id proteins are dominant negative regulators within the HLH family of proteins. In embryonic stem cells (ESCs), Id1 and Id3 maintain the pluripotent state by preventing neural differentiation. The Id1-interacting protein Zrf1 plays a crucial role as a chromatin-bound factor in specification of the neural fate from ESCs. Here, we show that Id1 blocks Zrf1 recruitment to chromatin, thus preventing the activation of neural genes during ESC differentiation. Moreover, genetic deletion of Id1 in ESCs caused misexpression of more than 6000 genes. Interestingly, the expression of almost half of those genes was restored upon further depletion of Zrf1. We therefore identified Zrf1 as a transcriptional regulator downstream of Id1 in ESCs. In Id1KO mESCs, Zrf1 expression was depleted by using shRNAs. Four replicates corresponding to four independent biological samples per group were collected.
2014-11-05 | E-GEOD-58627 | biostudies-arrayexpress
Project description:By combining RNAi-mediated knockdown of Id1 and Id3 in an aggressive mouse breast cancer cell line (4T1 cells) with genome-wide expression profiling, we identified several new Id target genes and novel pathways regulated by Id.
2020-10-31 | GSE129790 | GEO
Project description:Single cell RNA-Seq was performed on ID1 ID3 null endothelial cells to determine the effects of ID gene loss on endothelial cell maintainence and growth.
2020-04-22 | GSE149030 | GEO
Project description:Id1 and its closely related family member Id3 are expressed by a diversity of stem and progenitor cells. We show that Id1/3 are required for the self-renewal and proliferation of triple negative breast cancer (TNBC) cells both in vitro and in vivo. Furthermore, we identified that Id1/3 negatively regulates the tumour suppressor gene Robo1. Depletion of Robo1 could rescue the proliferative defect induced by Id1/3 knockdown. To understand the mechanisms by which Robo1 rescues cell proliferation in Id1/3 depleted cells, we performed RNA-Sequencing on 4T1 cells with Dox-inducible Id1/3 KD and/or Robo1 depletion using siRNA. We conclude that following Id1/3 knockdown, Robo1 is induced and exerts anti-proliferative effects via suppression of a Myc transcriptional program.
2020-10-31 | GSE129858 | GEO