Similar Datasets
Project description:A particular challenge hampering therapeutic advancements for high-risk sarcoma patients is the broad spectrum of molecularly distinct sarcoma entities and the corresponding lack of suitable model systems to recapitulate and study these diseases. To overcome this predicament, we developed a novel genetically-controlled, yet versatile mouse modeling platform allowing delivery of different genetic lesions by electroporation (EPO) of the thigh muscle in wildtype mice. This sarcoma EPO-GEMM (EPO-based genetically engineered mouse model) platform allowed the generation of ten biologically distinct sarcoma entities and subtypes on an isogenic background, including the first model of ETV6::NTRK3-driven infantile fibrosarcoma and of BCOR-inactivated rhabdomyosarcoma. Comprehensive histological and molecular profiling revealed that this mouse sarcoma cohort recapitulates the molecular diversity observed across the human disease with gene fusion and Trp53 status acting as major determinants of sarcoma biology. Integrative cross-species analyses confirmed faithful recapitulation of the human disease, including the expression of relevant immunotherapy targets.
2025-04-11 | GSE265873 | GEO
Project description:A particular challenge hampering therapeutic advancements for high-risk sarcoma patients is the broad spectrum of molecularly distinct sarcoma entities and the corresponding lack of suitable model systems to recapitulate and study these diseases. To overcome this predicament, we developed a novel genetically-controlled, yet versatile mouse modeling platform allowing delivery of different genetic lesions by electroporation (EPO) of the thigh muscle in wildtype mice. This sarcoma EPO-GEMM (EPO-based genetically engineered mouse model) platform allowed the generation of ten biologically distinct sarcoma entities and subtypes on an isogenic background, including the first model of ETV6::NTRK3-driven infantile fibrosarcoma and of BCOR-inactivated rhabdomyosarcoma. Comprehensive histological and molecular profiling revealed that this mouse sarcoma cohort recapitulates the molecular diversity observed across the human disease with gene fusion and Trp53 status acting as major determinants of sarcoma biology. Integrative cross-species analyses confirmed faithful recapitulation of the human disease, including the expression of relevant immunotherapy targets.
2025-04-11 | GSE265782 | GEO
Project description:Somatic muscle engineering faithfully recapitulates a molecular spectrum of high-risk sarcomas
| PRJNA1104601 | ENA
Project description:Somatic muscle engineering faithfully recapitulates a molecular spectrum of high-risk sarcomas [Illumina Array]
| PRJNA1104598 | ENA
Project description:Somatic muscle engineering faithfully recapitulates a molecular spectrum of high-risk sarcomas [RNA-Seq]
| PRJNA1104186 | ENA
Project description:Dominant gain-of-function alleles of Arabidopsis phytochrome B were recently shown to confer light-independent, constitutive photomorphogenic (cop) phenotypes to transgenic plants (Su and Lagarias, 2007). In the present study, comparative transcription profiling experiments were performed to assess whether the pattern of gene expression regulated by these alleles accurately reflects the process of photomorphogenesis in wild-type Arabidopsis. Whole-genome transcription profiles of dark-grown phyAphyB seedlings expressing the Y276H mutant of phyB (YHB) revealed that YHB reprograms about 13% of the Arabidopsis transcriptome in a light-independent manner. The YHB-regulated transcriptome proved qualitatively similar to but quantitatively greater than those of wild-type seedlings grown under 15 or 50 micromol m(-2) m(-1) continuous red light (Rc). Among the 2977 genes statistically significant two-fold (SSTF) regulated by YHB in the absence of light include those encoding components of the photosynthetic apparatus, tetrapyrrole/pigment biosynthetic pathways, and early light-responsive signaling factors. Approximately 80% of genes SSTF regulated by Rc were also YHB-regulated. Expression of a notable subset of 346 YHB-regulated genes proved to be strongly attenuated by Rc, indicating compensating regulation by phyC-E and/or other Rc-dependent processes. Since the majority of these 346 genes are regulated by the circadian clock, these results suggest that phyA- and phyB-independent light signaling pathway(s) strongly influence clock output. Together with the unique plastid morphology of dark-grown YHB seedlings, these analyses indicate that the YHB mutant induces constitutive photomorphogenesis via faithful reconstruction of phyB signaling pathways in a light-independent fashion.
| S-EPMC2639728 | biostudies-literature
Project description:Aim: To facilitate wide-scale implementation of Illumina Mouse Methylation BeadChip (MMB) technology, array-based measurement of cytosine methylation was compared with the gold-standard assessment of DNA methylation by whole-genome bisulfite sequencing (WGBS). Methods: DNA methylation across two mouse strains (C57B6 and C3H) and both sexes was assessed using the MMB and compared with previously existing deep-coverage WGBS of mice of the same strain and sex. Results & conclusion: The findings demonstrated that 93.3-99.2% of sites had similar measurements of methylation across technologies and that differentially methylated cytosines and regions identified by each technology overlap and enrich for similar biological functions, suggesting that the MMB faithfully recapitulates the findings of WGBS.
| S-EPMC10131490 | biostudies-literature
Project description:PurposeWe aimed to generate and phenotype a mouse model of foveal hypoplasia, optic nerve decussation defects, and anterior segment dysgenesis (FHONDA), a rare disease associated with mutations in Slc38a8 that causes severe visual alterations similar to albinism without affecting pigmentation.MethodsThe FHONDA mouse model was generated with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology using an RNA guide targeting the Scl38a8 murine locus. The resulting mice were backcrossed to C57BL/6J. Melanin content was measured using spectrophotometry. Retinal cell architecture was analyzed through light and electron microscopy. Retinal projections to the brain were evaluated with anterograde labelling in embryos and adults. Visual function was assessed by electroretinography (ERG) and the optomotor test (OT).ResultsFrom numerous Slc38a8 mouse mutant alleles generated, we selected one that encodes a truncated protein (p.196Pro*, equivalent to p.199Pro* in the human protein) closely resembling a mutant allele described in patients (p.200Gln*). Slc38a8 mutant mice exhibit wild-type eye and coat pigmentation with comparable melanin content. Subcellular abnormalities were observed in retinal pigment epithelium cells of Slc38a8 mutant mice. Anterograde labeling experiments of retinal projections in embryos and adults showed a reduction of ipsilateral fibers. Functional visual analyses revealed a decreased ERG response in scotopic conditions and a reduction of visual acuity in mutant mice measured by OT.ConclusionsSlc38a8 mutant mice recapitulate the phenotype of patients with FHONDA concerning their normal pigmentation and their abnormal visual system, in the latter being a hallmark of all types of albinism. These mice will be helpful in better understanding the pathophysiology of this genetic condition.
| S-EPMC10599165 | biostudies-literature
Project description:-7/del(7q) occurs in half of myeloid malignancies with adverse-risk cytogenetic features and is associated with poor survival. We identified the spectrum of mutations that co-occur with -7/del(7q) in 40 patients with de novo or therapy-related myeloid neoplasms. -7/del(7q) leukaemias have a distinct mutational profile characterized by low frequencies of alterations in genes encoding transcription factors, cohesin and DNA-methylation-related proteins. In contrast, RAS pathway activating mutations occurred in 50% of cases, a significantly higher frequency than other acute myeloid leukaemias and higher than previously reported. Our data provide guidance for which pathways may be most relevant in the treatment of adverse-risk myeloid leukaemia.
| S-EPMC5479678 | biostudies-literature
Project description:BackgroundHuman pluripotent stem cell-derived muscle models show great potential for translational research. Here, we describe developmentally inspired methods for the derivation of skeletal muscle cells and their utility in skeletal muscle tissue engineering with the aim to model skeletal muscle regeneration and dystrophy in vitro.MethodsKey steps include the directed differentiation of human pluripotent stem cells to embryonic muscle progenitors followed by primary and secondary foetal myogenesis into three-dimensional muscle. To simulate Duchenne muscular dystrophy (DMD), a patient-specific induced pluripotent stem cell line was compared to a CRISPR/Cas9-edited isogenic control line.ResultsThe established skeletal muscle differentiation protocol robustly and faithfully recapitulates critical steps of embryonic myogenesis in two-dimensional and three-dimensional cultures, resulting in functional human skeletal muscle organoids (SMOs) and engineered skeletal muscles (ESMs) with a regeneration-competent satellite-like cell pool. Tissue-engineered muscle exhibits organotypic maturation and function (up to 5.7 ± 0.5 mN tetanic twitch tension at 100 Hz in ESM). Contractile performance could be further enhanced by timed thyroid hormone treatment, increasing the speed of contraction (time to peak contraction) as well as relaxation (time to 50% relaxation) of single twitches from 107 ± 2 to 75 ± 4 ms (P < 0.05) and from 146 ± 6 to 100 ± 6 ms (P < 0.05), respectively. Satellite-like cells could be documented as largely quiescent PAX7+ cells (75 ± 6% Ki67- ) located adjacent to muscle fibres confined under a laminin-containing basal membrane. Activation of the engineered satellite-like cell niche was documented in a cardiotoxin injury model with marked recovery of contractility to 57 ± 8% of the pre-injury force 21 days post-injury (P < 0.05 compared to Day 2 post-injury), which was completely blocked by preceding irradiation. Absence of dystrophin in DMD ESM caused a marked reduction of contractile force (-35 ± 7%, P < 0.05) and impaired expression of fast myosin isoforms resulting in prolonged contraction (175 ± 14 ms, P < 0.05 vs. gene-edited control) and relaxation (238 ± 22 ms, P < 0.05 vs. gene-edited control) times. Restoration of dystrophin levels by gene editing rescued the DMD phenotype in ESM.ConclusionsWe introduce human muscle models with canonical properties of bona fide skeletal muscle in vivo to study muscle development, maturation, disease and repair.
| S-EPMC9745484 | biostudies-literature