RNA-Seq of fibrillin 1 (Fbn1) tight-skin (Tsk) mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA737339 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14803578.fastq.gz | Fastqsanger.gz | |||
| SRR14803579.fastq.gz | Fastqsanger.gz | |||
| SRR14803580.fastq.gz | Fastqsanger.gz | |||
| SRR14803581.fastq.gz | Fastqsanger.gz | |||
| SRR14803582.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:A fibrotic environment supports cancer growth. Our aim is to assess the transcriptomic differences by performing RNA sequencing in a fibrosis mouse model to provide insight into the increased growth of ovarian cancer in Fbn1 Tsk mice. Elucidating the targets important in fibrosis could provide potential clues to the mechanism of preferential cancer growth in fibrotic environments.
2024-06-11 | GSE178082 | GEO
Project description:Patients with systemic sclerosis have a significantly increased incidence of developing various solid malignancies within a few years of systemic sclerosis onset but the mechanism of tumor promotion is not well understood. The tight skin (TSK) mouse has been a valuable model for investigating systemic sclerosis-related pathologies due to increased extracellular matrix deposition, fibrosis in connective tissues, and altered immune cell activation. Despite the role of extracellular matrix and fibrosis in cancer progression, the potential of the TSK mouse as a model for cancer studies is unexplored. Our RNA sequencing analysis of adult dorsal skin samples from TSK and wild-type (WT) mice revealed a notable enrichment for genes typically associated with cancer aggressiveness and desmoplasia. To investigate the impact of the altered microenvironment in TSK mice on cancer progression, we compared the tumor-forming capabilities in TSK mice and WT mice using a syngeneic mouse model of ovarian cancer. TSK mice exhibited larger and more invasive subcutaneous and intraperitoneal tumors in comparison to WT controls, suggesting the role of the microenvironment in promoting cancer progression. Single-cell RNA sequencing analysis of tumors in TSK and WT mice revealed a higher neutrophil-to-lymphocyte ratio, and an enrichment in profibrotic subpopulations of myofibroblasts and macrophages in TSK mice.
2025-09-01 | GSE292228 | GEO
Project description:This study contains RNA-seq analysis of neonatal dermal fibroblasts from mice with Fbn1 G234D/G234D mutation to uncover its impact on ECM gene expression, potentially shedding light on the tight skin phenotype. While both wild-type (WT) and mutant fibroblasts showed differences, two of the mutants exhibited more significant changes, aligning with the early onset of the disease. These earlier data was deposited in GSE268383. In this study we added 2 more wild type fibroblasts and 3 more homozygous mutant cells to ascertain the features we obtained prevously. As previously noted, there was no obvious change in ECM and ECM-modifying genes, such as the LOX family, Fbn1, and TGFβ/BMP signaling genes; while the mutants displayed upregulation of muscle developmental genes (e.g., Myod1, Myog, Myh family), immune response, and cell-cell adhesion/cytoskeletal genes. In line with previous data, downregulated genes were still enriched for histone genes and developmental transcription factors, hinting at potential chromatin/transcriptional state modifications underlying the tight skin phenotype. These transcriptomic findings underscore the need for further investigation into the mechanobiological implications of Fbn1G234D/G234D fibroblasts.
2025-01-29 | GSE268383 | GEO
Project description:Patients with systemic sclerosis have a significantly increased incidence of developing various solid malignancies within a few years of systemic sclerosis onset but the mechanism of tumor promotion is not well understood. The tight skin (TSK) mouse has been a valuable model for investigating systemic sclerosis-related pathologies due to increased extracellular matrix deposition, fibrosis in connective tissues, and altered immune cell activation. Despite the role of extracellular matrix and fibrosis in cancer progression, the potential of the TSK mouse as a model for cancer studies is unexplored. Our RNA sequencing analysis of adult dorsal skin samples from TSK and wild-type (WT) mice revealed a notable enrichment for genes typically associated with cancer aggressiveness and desmoplasia. To investigate the impact of the altered microenvironment in TSK mice on cancer progression, we compared the tumor-forming capabilities in TSK mice and WT mice using a syngeneic mouse model of ovarian cancer. TSK mice exhibited larger and more invasive subcutaneous and intraperitoneal tumors in comparison to WT controls, suggesting the role of the microenvironment in promoting cancer progression. Single-cell RNA sequencing analysis of tumors in TSK and WT mice revealed a higher neutrophil-to-lymphocyte ratio, and an enrichment in profibrotic subpopulations of myofibroblasts and macrophages in TSK mice.
2024-04-08 | GSE255493 | GEO
Project description:Fibrillin-1 (FBN1) is the major component of extracellular matrix microfibrils, which are required for proper development of elastic tissues including heart and lung. Through protein-protein interactions with latent TGF-beta binding protein 1 (LTBP1), microfibrils assist regulation of TGF-beta signaling. Mutations within the 47 epidermal growth factor-like (EGF) repeats of FBN1 cause autosomal dominant disorders including Marfan Syndrome that disrupt TGF-beta signaling. We recently identified 2 novel protein O-glucosyltransferases, Protein O-glucosyltransferase 2 (POGLUT2) and Protein O-glucosyltransferase 3 (POGLUT3), that modify a few EGF repeats on Notch. Here, using mass spectral analysis, we show that POGLUT2 and POGLUT3 also modify over half of the EGF repeats on FBN1, fibrillin-2 (FBN2), and LTBP1. While most sites are modified by both enzymes, some sites show a preference for either POGLUT2 or POGLUT3. POGLUT2 and POGLUT3 are homologs of POGLUT1, which stabilizes Notch proteins by addition of O-glucose to Notch EGF repeats. Like POGLUT1, POGLUT2 and 3 can discern a folded versus unfolded EGF repeat, suggesting POGLUT2 and 3 are involved in a protein folding pathway. In vitro secretion assays using recombinant FBN1 revealed reduced FBN1 secretion in POGLUT2 knockout, POGLUT3 knockout, and POGLUT2 and 3 double knockout HEK293T cells compared to wild type. These results illustrate that POGLUT2 and 3 function together to O-glycosylate protein targets, and that these modifications play a role in secretion of target proteins.
2021-08-06 | PXD025725 | Pride
Project description:Patients with systemic sclerosis have a significantly increased incidence of developing various solid malignancies within a few years of systemic sclerosis onset but the mechanism of tumor promotion is not well understood. The tight skin (TSK) mouse has been a valuable model for investigating systemic sclerosis-related pathologies due to increased extracellular matrix deposition, fibrosis in connective tissues, and altered immune cell activation. Despite the role of extracellular matrix and fibrosis in cancer progression, the potential of the TSK mouse as a model for cancer studies is unexplored. Our RNA sequencing analysis of adult dorsal skin samples from TSK and wild-type (WT) mice revealed a notable enrichment for genes typically associated with cancer aggressiveness and desmoplasia. To investigate the impact of the altered microenvironment in TSK mice on cancer progression, we compared the tumor-forming capabilities in TSK mice and WT mice using a syngeneic mouse model of ovarian cancer. TSK mice exhibited larger and more invasive subcutaneous and intraperitoneal tumors in comparison to WT controls, suggesting the role of the microenvironment in promoting cancer progression. Single-cell RNA sequencing analysis of tumors in TSK and WT mice revealed a higher neutrophil-to-lymphocyte ratio, and an enrichment in profibrotic subpopulations of myofibroblasts and macrophages in TSK mice.
2025-09-01 | GSE292229 | GEO
Project description:Patients with systemic sclerosis have a significantly increased incidence of developing various solid malignancies within a few years of systemic sclerosis onset but the mechanism of tumor promotion is not well understood. The tight skin (TSK) mouse has been a valuable model for investigating systemic sclerosis-related pathologies due to increased extracellular matrix deposition, fibrosis in connective tissues, and altered immune cell activation. Despite the role of extracellular matrix and fibrosis in cancer progression, the potential of the TSK mouse as a model for cancer studies is unexplored. Our RNA sequencing analysis of adult dorsal skin samples from TSK and wild-type (WT) mice revealed a notable enrichment for genes typically associated with cancer aggressiveness and desmoplasia. To investigate the impact of the altered microenvironment in TSK mice on cancer progression, we compared the tumor-forming capabilities in TSK mice and WT mice using a syngeneic mouse model of ovarian cancer. TSK mice exhibited larger and more invasive subcutaneous and intraperitoneal tumors in comparison to WT controls, suggesting the role of the microenvironment in promoting cancer progression. Single-cell RNA sequencing analysis of tumors in TSK and WT mice revealed a higher neutrophil-to-lymphocyte ratio, and an enrichment in profibrotic subpopulations of myofibroblasts and macrophages in TSK mice.
2025-09-01 | GSE292227 | GEO
Project description:Patients with systemic sclerosis have a significantly increased incidence of developing various solid malignancies within a few years of systemic sclerosis onset but the mechanism of tumor promotion is not well understood. The tight skin (TSK) mouse has been a valuable model for investigating systemic sclerosis-related pathologies due to increased extracellular matrix deposition, fibrosis in connective tissues, and altered immune cell activation. Despite the role of extracellular matrix and fibrosis in cancer progression, the potential of the TSK mouse as a model for cancer studies is unexplored. Our RNA sequencing analysis of adult dorsal skin samples from TSK and wild-type (WT) mice revealed a notable enrichment for genes typically associated with cancer aggressiveness and desmoplasia. To investigate the impact of the altered microenvironment in TSK mice on cancer progression, we compared the tumor-forming capabilities in TSK mice and WT mice using a syngeneic mouse model of ovarian cancer. TSK mice exhibited larger and more invasive subcutaneous and intraperitoneal tumors in comparison to WT controls, suggesting the role of the microenvironment in promoting cancer progression. Single-cell RNA sequencing analysis of tumors in TSK and WT mice revealed a higher neutrophil-to-lymphocyte ratio, and an enrichment in profibrotic subpopulations of myofibroblasts and macrophages in TSK mice.
2024-04-08 | GSE255492 | GEO
Project description:Analysis of mouse Adamts6 and Adamts10 mutant embryos, lacking these homologous secreted metalloproteases individually and in combination, along with in vitro analysis of microfibrils, measurement of ADAMTS6-fibrillin affinities and N-terminomics determination of ADAMTS6-cleaved sites, demonstrates a transcriptionally adapted system for fibrillin-2 proteolysis that contributes to postnatal fibrillin-1 dominance. The lack of ADAMTS6, alone and in combination with ADAMTS10 led to excess fibrillin-2 in perichondrium, with impaired skeletal development. Although ADAMTS6 cleaves fibrillin-1 and fibrillin-2 as well as fibronectin, which provides the initial scaffold for microfibril assembly, primacy of the protease-substrate relationship between ADAMTS6 and fibrillin-2 was unequivocally established by reversal of these defects in Adamts6-/- embryos by genetic reduction of Fbn2, but not Fbn1.
2022-05-20 | PXD027096 | Pride
Project description:Duchenne muscular dystrophy (DMD) involves progressive muscle degeneration associated with calcium dysregulation, but the mechanisms linking extracellular matrix (ECM) integrity to calcium homeostasis remain unclear. We investigated whether MUA-3, a fibrillin-related ECM protein in Caenorhabditis elegans, contributes to calcium regulation in dystrophic muscle. Using fluorescent calcium imaging in transgenic worms expressing muscle-specific GCaMP2, we found that downregulating mua-3 selectively elevated resting calcium levels in healthy muscle but had no effect in dystrophic (dys-1) muscle, suggesting impaired MUA-3 function in dystrophy. Despite altered calcium dynamics, mua-3 downregulation did not affect locomotor function. In human dystrophic myoblasts, we observed significantly elevated sarcoplasmic calcium levels concurrent with substantial downregulation of fibrillin genes FBN1/FBN2. These findings demonstrate that fibrillin-related proteins regulate calcium homeostasis across species, suggesting that ECM integrity directly contributes to cellular calcium control in muscle. This work identifies a conserved mechanism linking extracellular matrix stability to intracellular calcium regulation and suggests that targeting ECM-calcium coupling may offer new therapeutic approaches for muscular dystrophy.
2025-09-01 | GSE299627 | GEO