Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21617400.fastq.gz | Fastqsanger.gz | |||
| SRR21617500.fastq.gz | Fastqsanger.gz | |||
| SRR21617600.fastq.gz | Fastqsanger.gz | |||
| SRR21617700.fastq.gz | Fastqsanger.gz | |||
| SRR21617800.fastq.gz | Fastqsanger.gz |
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Project description:Thoracic aortic aneurysms and dissections (TAAD), as occur in Marfan syndrome (MFS), currently lack a cure. Our previous studies revealed that overactivation of the AKT-NO signaling pathway mediates aortic disease in MFS. However, the mechanisms upstream of AKT activation remained poorly understood. Here we identify the Fibronectin-αVβ3-PI3K-PIP3-PDK1-ILK cascade as a critical mediator of AKT-NOS2 upregulation and aortic disease in MFS. We show that fibronectin (FN) accumulates in the walls of human and mouse MFS aortas. Disrupting FN multimerization inhibits AKT activation and NOS2 induction in vascular smooth muscle cells (VSMCs), prevents aortic contractility dysregulation, and reverses aortic dilation in MFS mice. Mechanistically, both human and mouse MFS aortas exhibit αVβ3 and ILK upregulation. Pharmacological inhibition of αVβ3, PI3K, PDK1, and ILK, or their recruitment to the plasma membrane by PIP3, prevents FN-induced AKT activation and NOS2 upregulation in VMSCs and aortic contractility dysregulation. Furthermore, ILK inhibition or aortic silencing reverses aortic disease, while its deletion in smooth muscle cells prevents aortic growth in MFS mice. These findings establish the most thoroughly characterized pathway implicated in MFS to date and suggest a causative role for the FN-αVβ3-PI3K-PIP3-PDK1-ILK-AKT-NOS2 cascade in human TAAD, highlighting its components as potential targets for therapeutic intervention.
2026-06-02 | PXD077940 | Pride
Project description:To better understand mechanisms of cell organization and function in the aortas of healthy and MFS patients, we performed single cell RNA sequencing (scRNA-seq) and label-free single-cell mass spectrometry35 in aortas isolated from healthy and MFS mice and human MFS aneurysm aortic tissue. We discovered new cell type specific proteins not regulated at the transcriptomic level in health and disease, including post-transcriptional regulation of FBN1 protein levels. Furthermore, we identified previously unrecognized cell-surface proteins that emerge as SMCs transition into a modulated phenotypic state in MFS mice. Comparison with a human MFS aortic root proteome demonstrated conservation of SMC associated protein networks across species, highlighting shared molecular features of vascular remodeling.
2026-09-14 | PXD078860 | Pride
Project description:Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) are genetically complex soft tissue sarcomas with distinct morphological features. Treatment typically involves surgery, often combined with neoadjuvant chemo- or radiotherapy. To better understand the immunobiology of these sarcomas and its associations with treatment response and prognosis, we performed transcriptomic and immunophenotypic profiling. RNA sequencing was performed on 13 UPS and 10 MFS, and immunological profiles were compared with soft tissue sarcoma data from The Cancer Genome Atlas (n = 206 including 44 UPS and 17 MFS). Immune contextures were further evaluated in 14 UPS and 15 MFS using imaging mass cytometry. Characterization of T cell and macrophage infiltration in tumors was further assessed in 23 UPS and 22 MFS through multispectral immunofluorescence and immunohistochemical analysis. UPS and MFS demonstrated immunogenic features compared to other soft tissue sarcomas, with subsets of UPS and MFS demonstrating high T cell infiltration, while UPS demonstrated a higher infiltration by myeloid cells as compared to MFS. Prognostically, T cells and CD68+CD163+ macrophages were associated with metastasis-free survival in UPS but not in MFS. Notably, in UPS, neoadjuvant radiotherapy appeared to induce cytotoxic T cell infiltration and depletion of myeloid cells, whereas these effects were not observed in MFS. These findings highlight important differences in the immunobiology of UPS and MFS with therapeutic and prognostic implications. These differences should be taken into account given the growing availability of immunotherapeutic options for treating patients with soft tissue sarcomas.
2025-06-30 | GSE285944 | GEO
Project description:Analysis of gene expression comparison between MFS- and mcMFS-SMCs Total RNA was isolated from MFS- and mcMFS-SMCs, differentiated from equivalent induced pluripotent cells (iPSCs)
2016-03-03 | E-GEOD-78833 | biostudies-arrayexpress
Project description:high throughput sequencing of the metagenome of mexican children
2020-03-16 | GSE143207 | GEO
Project description:Fibrillin dysfunction in Marfan syndrome (MFS) causes severe cardiovascular complications, including aortic dilation, dissection, and rupture. To model MFS, we generated zebrafish mutants lacking various fibrillin genes. Among them, fibrillin-2b-deficient zebrafish exhibited cardiovascular phenotypes resembling those seen in patients with MFS. Multimodal imaging revealed early cardiac defects, bulbus arteriosus dilation, and valve abnormalities. RNA sequencing identified developmental disruptions, and compound testing demonstrated the model’s potential for drug discovery. This zebrafish model, recapitulating key cardiovascular features of MFS, provides a valuable platform for investigating disease mechanisms and identifying novel treatment strategies.
2025-06-27 | GSE300393 | GEO
Project description:Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 (Fbn1) gene. While aortic rupture is the major cause of mortality in MFS, patients also suffer from poorly understood pulmonary complications. Loss of basal nitric oxide (NO) production and vascular integrity are proposed to take part in MFS aortic root disease, yet their contribution to lung complications has yet to be determined. Due to its capacity to potentiate the vasodilatory NO/cyclic guanylate monophosphate signaling pathway, we assessed whether the phosphodiesterase-5 (PDE5) inhibitor sildenafil (SIL) could attenuate aortic root remodelling and emphysema in a mouse model of MFS. Despite increasing NO-dependent vasodilation, SIL unexpectedly elevated mean arterial blood pressure, failed to inhibit MFS aortic root dilation and exacerbated elastic fibrefiber fragmentation. In the lung, early pulmonary artery dilation observed in untreated MFS mice was delayed by SIL treatment, and severe emphysema-like alveolar destruction was prevented. In addition, improvements in select parameters of lung function were documented. Subsequent micro-array analyses showed changes to gene signatures involved in the inflammatory response in MFS lung treated with SIL, without significant downregulation of connective tissue or TGF-β signalling genes. Since PDE5 inhibition leads to improved lung histopathology and function, the effects of SIL against emphysema warrant further investigation in the settings of MFS despite limited efficacy on aortic root remodelling.
2019-03-19 | GSE128481 | GEO
Project description:The central nervous system (CNS) is surrounded by three membranes called meninges. Specialized fibroblasts, originating from the mesoderm and neural crest, primarily populate the meninges and serve as a binding agent. Our goal was to compare fibroblasts from meninges and skin obtained from the same human-aged donors, exploring their molecular and cellular characteristics related to CNS functions. We isolated meningeal fibroblasts (MFs) and skin fibroblasts (SFs) from brain donors. A functional analysis was performed measuring cell appearance, metabolic activity, and cellular orientation. We examined fibronectin, serpin H1, β-III-tubulin, and nestin through qPCR and immunofluorescence. A whole transcriptome analysis was also performed to characterize the gene expression of MFs and SFs. MFs appeared more rapidly post-tissue processing, while SFs have an elevated cellular metabolism and a well-defined cellular orientation. The four markers were mostly similar between the MFs and SFs, except for nestin, more expressed in MFs. Transcriptome analysis reveals significant differences, particularly in cyclic adenosine monophosphate (cAMP) metabolism and response to forskolin, both of which are upregulated in MFs. This study highlights MFs' unique characteristics, such as the timing of appearance, metabolic activity, and gene expression patterns, particularly in cAMP metabolism and response to forskolin. These findings contribute to a deeper understanding of non-neuronal cells' involvement in CNS activities and potentially open avenues for therapeutic exploration.
2024-02-29 | GSE255684 | GEO
Project description:Thoracic aortic aneurysm (TAAs) are a severe complication in Marfan Symdrome (MFS), often leading to dissection and premature death. To identify potential drug targets for the treatment for TAAs we used gene expression profiles from MFS mice and patients to predict kinases that regulate gene expression. Among the top predictions was the kinase HIPK2. Ubiquitous post-natal inactivation of the HIPK2 gene, as well as chronic administration of an allosteric inhibitor of HIPK2/Smad3 interaction, increased the survival of MFS mice and improved multiple surrogate parameters.
2021-10-27 | GSE145903 | GEO
Project description:Bacillus thuringiensis strain:BT-MFS Genome sequencing
| PRJNA1527648 | ENA