ArticleHuman molecular genetics2018
A patient-derived iPSC model revealed oxidative stress increases facioscapulohumeral muscular dystrophy-causative DUX4.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- Elevated labile iron contributes to membrane repair deficits in facioscapulohumeral muscular dystrophy.iScience · 2026Article
- Transgenic mouse models for investigating human DUX4 expression during development and its roles in FSHD pathophysiology.Disease models & mechanisms · 2026Article
- FBXO22 Suppresses Oxidative Stress-Induced ASK1 Activation and Cell Death via Ubiquitination-Dependent Degradation of TRIM48.International journal of molecular sciences · 2025Article
- Diversity challenges and reconciles genetics in facioscapulohumeral muscular dystrophy.Journal of human genetics · 2025Review
- DUX4 at 25: how it emerged from "junk DNA" to become the cause of facioscapulohumeral muscular dystrophy.Skeletal muscle · 2025Review
- Early and non-destructive prediction of the differentiation efficiency of human induced pluripotent stem cells using imaging and machine learning.Scientific reports · 2025Article
- The Unexplored Role of Connexin Hemichannels in Promoting Facioscapulohumeral Muscular Dystrophy Progression.International journal of molecular sciences · 2025Review
- In Vitro Evaluation of Exon Skipping in Disease-Specific iPSC-Derived Myocytes.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Muscle Proteome Analysis of Facioscapulohumeral Dystrophy Patients Reveals a Metabolic Rewiring Promoting Oxidative/Reductive Stress Contributing to the Loss of Muscle Function.Antioxidants (Basel, Switzerland) · 2024Article
- Engineered FSHD mutations results in D4Z4 heterochromatin disruption and feedforward DUX4 network activation.iScience · 2024Article
- The DUX4-HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected.International journal of molecular sciences · 2024Article
- snRNA-seq analysis in multinucleated myogenic FSHD cells identifies heterogeneous FSHD transcriptome signatures associated with embryonic-like program activation and oxidative stress-induced apoptosis.Human molecular genetics · 2024Article
- Advancements in 2D and 3D In Vitro Models for Studying Neuromuscular Diseases.International journal of molecular sciences · 2023Review
- Article
- Induced Pluripotent Stem Cells for Tissue-Engineered Skeletal Muscles.International journal of molecular sciences · 2023Review
- Article
- Facioscapulohumeral muscular dystrophy: the road to targeted therapies.Nature reviews. Neurology · 2023Review
- Establishment of quantitative and consistent in vitro skeletal muscle pathological models of myotonic dystrophy type 1 using patient-derived iPSCs.Scientific reports · 2023Article
- Induced Pluripotent Stem Cells for Modeling Physiological and Pathological Striated Muscle Complexity.Journal of neuromuscular diseases · 2023Review
- Whole-muscle fat analysis identifies distal muscle end as disease initiation site in facioscapulohumeral muscular dystrophy.Communications medicine · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Double homeobox 4 (DUX4), the causative gene of facioscapulohumeral muscular dystrophy (FSHD), is ectopically expressed in the skeletal muscle cells of FSHD patients because of chromatin relaxation at 4q35. The diminished heterochromatic state at 4q35 is caused by either large genome contractions [FSHD type 1 (FSHD1)] or mutations in genes encoding chromatin regulators, such as SMCHD1 [FSHD type 2 (FSHD2)]. However, the mechanism by which DUX4 expression is regulated remains largely unknown. Here, using a myocyte model developed from patient-derived induced pluripotent stem cells, we determined that DUX4 expression was increased by oxidative stress (OS), a common environmental stress in skeletal muscle, in both FSHD1 and FSHD2 myocytes. We generated FSHD2-derived isogenic control clones with SMCHD1 mutation corrected by clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated 9 (Cas9) and homologous recombination and found in the myocytes obtained from these clones that DUX4 basal expression and the OS-induced upregulation were markedly suppressed due to an increase in the heterochromatic state at 4q35. We further found that DNA damage response (DDR) was involved in OS-induced DUX4 increase and identified ataxia-telangiectasia mutated, a DDR regulator, as a mediator of this effect. Our results suggest that the relaxed chromatin state in FSHD muscle cells permits aberrant access of OS-induced DDR signaling, thus increasing DUX4 expression. These results suggest OS could represent an environmental risk factor that promotes FSHD progression.
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