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Molecular insights into the role of desmin intermediate filament network in chromatin landscape, cardiomyocyte differentiation, and maturation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE274613 | GEO | 2025/09/17

REPOSITORIES: GEO

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Molecular Insights into the Role of Desmin Intermediate Filament Network in Chromatin Landscape, Early Cardiogenic Commitment and Cardiomyocyte Differentiation and Maturation (HiC)

Project description:The cardiac cytoskeleton is essential for the proper intracellular and intercellular integration of structure and function, failure of which leads to heart disease. However, its role during development and cardiac differentiation is often overlooked. Here, we sought to understand the role of the desmin intermediate filament cytoskeletal network in cardiac cell differentiation and homeostasis during embryonic development, post birth, adulthood and upon different stimuli. We show that desmin is highly expressed in cardiac progenitor cell populations during embryogenesis. In addition, using direct cellular reprogramming of fibroblasts to induced cardiomyocytes, we demonstrated that ectopic desmin expression directly influences cardiomyogenesis through a timely transcriptional regulation of the Notch1 signaling pathway. On the contrary, the absence of desmin in induced cardiomyocytes leads to substantial perturbations in cardiac maturation by diminishing the expression and proper localization of cardiac specific proteins, impairing calcium homeostasis and delaying myofibril formation. RNA and ChIP sequencing, along with chromosome conformation capture (HiC) in desmin-depleted cardiomyocytes revealed that the observed gene expression changes reflect the identified corresponding changes in chromatin architecture that cause loss of genome organization and thus contributing to pathophysiological phenotype.

2025-09-17 | GSE274607 | GEO

Molecular Insights into the Role of Desmin Intermediate Filament Network in Chromatin Landscape, Early Cardiogenic Commitment and Cardiomyocyte Differentiation and Maturation (RNA-Seq)

2025-09-17 | GSE274611 | GEO

Molecular Insights into the Role of Desmin Intermediate Filament Network in Chromatin Landscape, Early Cardiogenic Commitment and Cardiomyocyte Differentiation and Maturation (ChIP-Seq)

2025-09-17 | GSE274610 | GEO

Molecular Insights into the Role of Desmin Intermediate Filament Network in Chromatin Landscape, Early Cardiogenic Commitment and Cardiomyocyte Differentiation and Maturation (RNA-Seq Kap)

2025-09-17 | GSE274612 | GEO

Molecular insights into the role of desmin intermediate filament network in chromatin landscape, cardiomyocyte differentiation, and maturation

Project description:Molecular insights into the role of desmin intermediate filament network in chromatin landscape, cardiomyocyte differentiation, and maturation

| PRJNA1147278 | ENA

Molecular Insights into the Role of Desmin Intermediate Filament Network in Chromatin Landscape, Early Cardiogenic Commitment and Cardiomyocyte Differentiation and Maturation (HiC)

Project description:Molecular Insights into the Role of Desmin Intermediate Filament Network in Chromatin Landscape, Early Cardiogenic Commitment and Cardiomyocyte Differentiation and Maturation (HiC)

| PRJNA1147274 | ENA

Molecular Insights into the Role of Desmin Intermediate Filament Network in Chromatin Landscape, Early Cardiogenic Commitment and Cardiomyocyte Differentiation and Maturation (ChIP-Seq)

| PRJNA1147283 | ENA

Molecular Insights into the Role of Desmin Intermediate Filament Network in Chromatin Landscape, Early Cardiogenic Commitment and Cardiomyocyte Differentiation and Maturation (RNA-Seq)

| PRJNA1147287 | ENA

Molecular Insights into the Role of Desmin Intermediate Filament Network in Chromatin Landscape, Early Cardiogenic Commitment and Cardiomyocyte Differentiation and Maturation (RNA-Seq Kap)

| PRJNA1147285 | ENA

Desmuslin, an intermediate filament protein that interacts with alpha -dystrobrevin and desmin.

Project description:Dystrobrevin is a component of the dystrophin-associated protein complex and has been shown to interact directly with dystrophin, alpha1-syntrophin, and the sarcoglycan complex. The precise role of alpha-dystrobrevin in skeletal muscle has not yet been determined. To study alpha-dystrobrevin's function in skeletal muscle, we used the yeast two-hybrid approach to look for interacting proteins. Three overlapping clones were identified that encoded an intermediate filament protein we subsequently named desmuslin (DMN). Sequence analysis revealed that DMN has a short N-terminal domain, a conserved rod domain, and a long C-terminal domain, all common features of type 6 intermediate filament proteins. A positive interaction between DMN and alpha-dystrobrevin was confirmed with an in vitro coimmunoprecipitation assay. By Northern blot analysis, we find that DMN is expressed mainly in heart and skeletal muscle, although there is some expression in brain. Western blotting detected a 160-kDa protein in heart and skeletal muscle. Immunofluorescent microscopy localizes DMN in a stripe-like pattern in longitudinal sections and in a mosaic pattern in cross sections of skeletal muscle. Electron microscopic analysis shows DMN colocalized with desmin at the Z-lines. Subsequent coimmunoprecipitation experiments confirmed an interaction with desmin. Our findings suggest that DMN may serve as a direct linkage between the extracellular matrix and the Z-discs (through plectin) and may play an important role in maintaining muscle cell integrity.

| S-EPMC33438 | biostudies-literature

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