Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1313348 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Loeys Dietz Syndrome (LDS) is a connective tissue disorder caused by mutations along the TGF-beta signaling pathway and characterized by severe aortic aneurysm and craniofacial anomalies. Patients with LDS Type II (LDS2), caused by mutations in the TGFBR2 gene also exhibit enamel defects. A mouse model for LDS2, harboring a G357W mutation in the Tgfbr2 gene, recapitulates the cardiovascular, craniofacial and dental phenotype of the disease. As part of our transcriptomic analysis aimed at identifying genes that are differentially regulated in the enamel organ of Tgfbr2-G357W/+ mice at postnatal day 11, we peformed a similar analysis on the aorta transcriptome at the same age. Total RNA was extracted from aortic arches from six Tgfbr2-G357W/+ mice (LDS2, Het) and five Tgfbr2-+/+ wild-type littermates (WT). This dataset provides a comprehensive list of genes affected in the aorta of an LDS2 mouse model at a young age.
2025-06-06 | GSE226611 | GEO
Project description:Loeys-Dietz Syndrome (LDS), caused by a spectrum of mutations in the TGF-β signaling cascade, leads to aggressive thoracic aneurysms. Given the ubiquitous nature of TGF-β signaling machinery, the exact cell type(s) responsible for initiation of LDS pathogenesis is poorly understood.
2025-04-23 | GSE235678 | GEO
Project description:Loeys-Dietz Syndrome (LDS), caused by a spectrum of mutations in the TGF-β signaling cascade, leads to aggressive thoracic aneurysms. Given the ubiquitous nature of TGF-β signaling machinery, the exact cell type(s) responsible for initiation of LDS pathogenesis is poorly understood.
2025-03-25 | GSE288084 | GEO
Project description:Loeys-Dietz Syndrome (LDS), caused by a spectrum of mutations in the TGF-β signaling cascade, leads to aggressive thoracic aneurysms. Given the ubiquitous nature of TGF-β signaling machinery, the exact cell type(s) responsible for initiation of LDS pathogenesis is poorly understood.
2025-03-25 | GSE235638 | GEO
Project description:The Loeys-Dietz syndrome (LDS) is an inherited connective tissue disorder caused by mutations in the transforming growth factor β (TGF-β) receptors TGFBR1 or TGFBR2. Most patients with LDS develop severe aortic aneurysms resulting in early need of surgical intervention. We investigated circulating outgrowth endothelial cells (OEC) from the peripheral blood of LDS to gain further insight into the pathophysiology of the disorder. We performed gene expression profiling using microarray analysis followed by quantitative PCR for verification of gene expression. OECs isolated from age- and sex-matched healthy donors served as reference control. 3 OEC clones from different LDS patients were compared to their respective age- and sex-matched OEC clone isolated from healthy donors.
2013-06-27 | E-GEOD-38961 | biostudies-arrayexpress
Project description:Loeys Dietz Syndrome (LDS) is a connective tissue disorder caused by mutations along the TGF-beta signaling pathway and characterized by severe aortic aneurysm and craniofacial anomalies. Patients with LDS Type II (LDS2), caused by mutations in the TGFBR2 gene also exhibit enamel defects. A mouse model for LDS2, harboring a G357W mutation in the Tgfbr2 gene, recapitulates the cardiovascular, craniofacial and dental phenotype of the disease. This transcriptomic analysis aimed at identifying genes that are differentially regulated in first molars of Tgfbr2-G357W/+ mice at postnatal day 5 and 11. Total RNA was extracted from enamel organs from Tgfbr2-G357W/+ mice (LDSR2, KI) and Tgfbr2-+/+ wild-type littermates (WT).
2025-06-06 | GSE284226 | GEO
Project description:Loeys-Dietz syndrome (LDS) is a hereditary aneurysm disorder caused by mutations that impair transforming growth factor-β (TGF-β) signaling. Although LDS patients develop aneurysms throughout the arterial tree, the aortic root is a site of increased risk. In order to identify molecular determinants of this regional vulnerability, we investigated the transcriptional heterogeneity of vascular smooth muscle cells (VSMCs) in the aorta of Tgfbr1M318R/+ LDS mouse models by single cell RNA sequencing (scRNAseq) and spatial transcriptomics. Downregulation of transcripts coding for components of the extracellular matrix-receptor mechanosensing apparatus and upregulation of transcripts related to stress and inflammation were observed in all Tgfbr1M318R/+ VSMCs. However, regardless of genotype, a subset of Gata4-expressing VSMCs predominantly located in the aortic root intrinsically displayed a less differentiated, pro-inflammatory transcriptional profile. A similar population was also identified in a published scRNAseq dataset of the aorta of LDS patients via the Coordinated Gene Activity in Pattern Sets (CoGAPS)/ProjectR pipeline. Postnatal VSMC-specific Gata4 deletion resulted in reduced aortic root dilation in LDS mice, in association with decreased levels of Agtr1a and other pro-inflammatory regulators. We propose that widespread dysregulation of mechanosensitive pathways may act on regionally restricted factors that “prime” specific aortic locations to increased risk of aneurysm.
2024-06-28 | GSE267204 | GEO
Project description:The Loeys-Dietz syndrome (LDS) is an inherited connective tissue disorder caused by mutations in the transforming growth factor β (TGF-β) receptors TGFBR1 or TGFBR2. Most patients with LDS develop severe aortic aneurysms resulting in early need of surgical intervention. We investigated circulating outgrowth endothelial cells (OEC) from the peripheral blood of LDS to gain further insight into the pathophysiology of the disorder. We performed gene expression profiling using microarray analysis followed by quantitative PCR for verification of gene expression. OECs isolated from age- and sex-matched healthy donors served as reference control.
2013-06-27 | GSE38961 | GEO
Project description:Loeys Dietz Syndrome (LDS) is a connective tissue disorder caused by mutations along the TGF-beta signaling pathway and characterized by severe aortic aneurysm and craniofacial anomalies. Patients with LDS Type II (LDS2), caused by mutations in the TGFBR2 gene also exhibit enamel defects. A mouse model for LDS2, harboring a G357W mutation in the Tgfbr2 gene, recapitulates the cardiovascular, craniofacial and dental phenotype of the disease. This transcriptomic analysis aimed at identifying genes that are differentially regulated in the enamel organ of Tgfbr2-G357W/+ mice at postnatal day 11. Total RNA was extracted from enamel organs from five Tgfbr2-G357W/+ mice (LDSR2, KI) and eight Tgfbr2-+/+ wild-type littermates (WT). This dataset indicates that the mutation in Tgfbr2 in the enamel organ minimally affects gene expression and suggests that the enamel phenotype in LDS2 is not dependent on canonical TGF-beta signaling.
2025-06-06 | GSE226610 | GEO
Project description:Immunoglobulin E (IgE) is a potent mediator of allergic diseases, but the mechanisms that regulate IgE responses to innocuous environmental and food antigens remain unclear. Patients with Loeys-Dietz syndrome (LDS) who have mutations in genes encoding the TGFβ receptor are predisposed to IgE-mediated disorders. Here, using patient samples and a mouse model, we demonstrate that LDS mutations lead to reduced canonical TGFβ signaling, elevated total and allergen-specific IgE, increased type 2 follicular helper T cells (Tfh2), and exaggerated germinal center activity that was not prevented by the presence of wild type T regulatory cells. T cell intrinsic defects in LDS mice resulted in spontaneous sensitization to orally administered OVA, and inhibition of mammalian target of rapamycin (mTOR) prevented the exaggerated Tfh and IgE responses to OVA. Thus, TGFβ limits human and mouse Tfh2 cell development via the phosphatidylinositol-3-OH kinase gamma (PI3Kg)/AKT/mTOR pathway, and disruption of this pathway promotes allergic inflammation.
2023-08-01 | GSE202688 | GEO