McCune Mosaicism
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ABSTRACT:
PROVIDER: PRJEB71103 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Fibrous dysplasia (FD) and cemento-ossifying fibroma (COF) are benign fibrous-osseous lesions of the maxillofacial bones that exhibit numerous similarities in their clinicopathological aspects. However, due to differences in their clinical evolution and treatment, it is essential to diagnose these diseases with accuracy. The differences in the pathogeneses of FD and COF are largely unknown and currently there is no biomarker available for their differential diagnosis. Nonetheless, there are few studies comparing these lesions and predominantly comprised of immunohistochemical investigations of traditional bone biomarkers. Therefore, the present study aimed to quantitatively compare the proteomic and phosphoproteomic profiles of cemento-ossifying fibroma and fibrous dysplasia to shed light onto the mechanisms involved in their molecular pathogenesis and identify potential differential diagnosis biomarkers.
2022-03-14 | PXD030818 | Pride
Project description:Fibrous dysplasia (FD) is a rare bone disorder characterized by the replacement of normal bone with benign fibro-osseous tissue. Developments in our understanding of the pathophysiology and treatment options are impeded by the lack of suitable research models. In this study, we developed an in vitro organotypic model capable of recapitulating key intrinsic and phenotypic properties of FD. Transcriptomic profiling of individual cells isolated from patient lesional tissues revealed extensive intralesional molecular and cellular heterogeneity, indicative of pathogenic fibrotic processes.
2024-04-23 | GSE263294 | GEO
Project description:Chronic infantile neurological cutaneous and articular (CINCA) syndrome is an IL-1-driven autoinflammatory disorder caused mainly by NLRP3 mutations. The pathogenesis of CINCA syndrome patients who carry NLRP3 mutations as somatic mosaicism has not been precisely described because of the difficulty in separating individual cells based on the presence or absence of the mutation. Here, we report the generation of NLRP3-mutant and non-mutant induced pluripotent stem cell (iPSC) lines from two CINCA syndrome patients with somatic mosaicism, and describe their differentiation into macrophages (iPS-MPs). We found that mutant cells are predominantly responsible for the pathogenesis in these mosaic patients because only mutant iPS-MPs showed the disease relevant phenotype of abnormal IL-1β secretion. We also confirmed that the existing anti-inflammatory compounds inhibited the abnormal IL-1β secretion, indicating that mutant iPS-MPs are applicable for drug screening for CINCA syndrome and other NLRP3-related inflammatory conditions. Our results illustrate that patient-derived iPSCs are useful for dissecting somatic mosaicism, and that NLRP3-mutant iPSCs can provide a valuable platform for drug discovery for multiple NLRP3-related disorders.
2012-06-11 | GSE38626 | GEO
Project description:Chronic infantile neurological cutaneous and articular (CINCA) syndrome is an IL-1-driven autoinflammatory disorder caused mainly by NLRP3 mutations. The pathogenesis of CINCA syndrome patients who carry NLRP3 mutations as somatic mosaicism has not been precisely described because of the difficulty in separating individual cells based on the presence or absence of the mutation. Here, we report the generation of NLRP3-mutant and non-mutant induced pluripotent stem cell (iPSC) lines from two CINCA syndrome patients with somatic mosaicism, and describe their differentiation into macrophages (iPS-MPs). We found that mutant cells are predominantly responsible for the pathogenesis in these mosaic patients because only mutant iPS-MPs showed the disease relevant phenotype of abnormal IL-1M-NM-2 secretion. We also confirmed that the existing anti-inflammatory compounds inhibited the abnormal IL-1M-NM-2 secretion, indicating that mutant iPS-MPs are applicable for drug screening for CINCA syndrome and other NLRP3-related inflammatory conditions. Our results illustrate that patient-derived iPSCs are useful for dissecting somatic mosaicism, and that NLRP3-mutant iPSCs can provide a valuable platform for drug discovery for multiple NLRP3-related disorders. To characterize iPS and differentiated cells, RNA expression profiles were evaluated by microarray analysis.We analyzed iPC cells and macrophage from healthy volunteers and CINCA syndrome patients. Human ES cella and fibroblasts were used as control.
2012-06-10 | E-GEOD-38626 | biostudies-arrayexpress
Project description:In order to dissect pathways enchained in skeletal stem/progenitors by Fibrous Dysplasia mutations, we engineered human skeletal stem/progenitors with the mutation and performed transcriptomic analysis. FD mutation profoundly alters the properties of skeletal stem/progenitors by pushing hBMSCs towards formation of disorganized bone with a concomitant lack of fat development. In addition, the mutation created an altered in trans environment that pushed the overall system towards neovascularization, inflammation and osteoclastogenesis. We used microarrays to detail the global programme of gene expressionc of human skeletal progenitors containing the Gsα activating mutation R201C
2018-07-01 | GSE109818 | GEO
Project description:Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants in GNAS, encoding for Gαs, which leads to excessive cAMP signaling in bone marrow stromal cells (BMSCs). Despite advancements in our understanding of FD pathophysiology, the effect of Gαs activation in the BMSC transcriptome remains unclear, as well as how this translates into their local influence in the lesional microenvironment. In this study, we analyzed changes induced by Gαs activation in BMSC transcriptome and performed a comprehensive analysis of their production of cytokines and other secreted factors. We performed RNAseq of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, and combined their transcriptomic profiles to build a robust FD BMSC genetic signature. Pathways related to Gαs activation, cytokine signaling, and extracellular matrix deposition were identified. In addition, a comprehensive profile of their secreted cytokines and other factors was performed to identify modulation of several key factors we hypothesized to be involved in FD pathogenesis. We also screened circulating cytokines in a collection of plasma samples from patients with FD, finding positive correlations of several cytokines to their disease burden score, as well as to one another and bone turnover markers. Overall, these data support a pro-inflammatory, pro-osteoclastic behavior of BMSCs bearing hyperactive Gαs variants, and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.
2024-04-29 | GSE261359 | GEO
Project description:Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants in GNAS, encoding for Gαs, which leads to excessive cAMP signaling in bone marrow stromal cells (BMSCs). Despite advancements in our understanding of FD pathophysiology, the effect of Gαs activation in the BMSC transcriptome remains unclear, as well as how this translates into their local influence in the lesional microenvironment. In this study, we analyzed changes induced by Gαs activation in BMSC transcriptome and performed a comprehensive analysis of their production of cytokines and other secreted factors. We performed RNAseq of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, and combined their transcriptomic profiles to build a robust FD BMSC genetic signature. Pathways related to Gαs activation, cytokine signaling, and extracellular matrix deposition were identified. In addition, a comprehensive profile of their secreted cytokines and other factors was performed to identify modulation of several key factors we hypothesized to be involved in FD pathogenesis. We also screened circulating cytokines in a collection of plasma samples from patients with FD, finding positive correlations of several cytokines to their disease burden score, as well as to one another and bone turnover markers. Overall, these data support a pro-inflammatory, pro-osteoclastic behavior of BMSCs bearing hyperactive Gαs variants, and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.
2024-04-29 | GSE261358 | GEO
Project description:Chromosome X Mosaicism Methylation Study
| PRJNA320447 | ENA
Project description:Genetic variation is responsible for the generation of phenotypic diversity, including susceptibility to disease. Two major types of variation are known: single nucleotide polymorphisms (SNPs) and a more recently discovered structural variation, involving changes in copy number (CNVs) of kilobase- to megabase-sized chromosomal segments. Variation caused by CNVs has exceeded the amount of SNP-based differences expected to exist between two unrelated humans. Furthermore, many CNVs have been associated with disease predisposition. It is unknown whether CNVs arise in somatic cells, but it is, however, generally assumed that normal cells are genetically identical. Here we show that CNVs are frequent in healthy somatic cells of adult humans. We tested 34 tissue samples from three subjects and, having analyzed for each tissue <10-6 of all cells expected in an adult human, we observed at least six CNVs, affecting a single organ or one or more tissues of the same subject. The CNVs ranged from 82-176 kb, often encompassing known genes, potentially affecting gene function. Our results point to a paradigm shift in the genetics of somatic cells and indicate that humans are commonly affected by somatic mosaicism for stochastic CNVs, which occur in a substantial fraction of cells. A considerable number of phenotypes and diseases affecting humans are a consequence of a somatic process. Thus, our conclusions will be important for the delineation of genetic factors behind these phenotypes. Consequently, biobanks should consider sampling multiple tissues in order to better address mosaicism in the studies of somatic disorders. Furthermore, forensic medicine laboratories should be sensitized to the issue of underestimated frequency of somatic CNV mosaicism. Keywords: copy number variation (CNV), phenotype diversity, somatic cells
2008-09-16 | GSE9598 | GEO