Yassemi Capetanaki, Mary Tsikitis and their colleagues recently published a study in the journal Cell Death & Disease

Tsikitis et al 2025
Studies by Tsikitis and colleagues unraveled an unexpected role of the muscle specific desmin intermediate filament (IF) cytoskeletal network in the regulation of cardiac gene expression responsible for  cardiomyocyte determination, differentiation and maturation. The desmin IF cytoskeleton  forms a continuous  network that links the contractile apparatus with the plasma membrane, membranous organelles, and the nucleus. Importantly,  the desmin cytoskeleton forms a continuous network with the nuclear lamin  IF  cytoskeleton, thus allowing the formation of physical and functional continuum that provides the structural basis for functional coordination among all cellular compartments, including  mechanotransduction to the nucleus. The latter mechanobiological signaling is very crucial in muscle cells, where it governs gene expression programs responsible for defining muscle identity, differentiation, regeneration, maintenance, and contractile function. In this study, Tsikitis et al. provided strong molecular evidence elucidating how the desmin IF network directly influences the chromatin landscape and the epigenetic regulation of cardiomyocyte differentiation and maturation. Their findings demonstrate that desmin modulates chromatin accessibility and spatial organization, thereby influencing cardiomyocyte specific transcriptional programs that drive the transition from progenitor to mature cardiomyocyte states. Together with previous data, the present studies establish the desmin IF network as a central mechanobiological and regulatory platform that not only maintains cellular and tissue integrity but also integrates mechanical, structural, and epigenetic information to control gene expression, differentiation, and cardiac homeostasis. Disruption of this continuum—through genetic mutations or acquired stress—compromises the mechanical-nuclear coupling and transcriptional regulation essential for cardiac muscle maintenance, ultimately contributing to the onset and progression of cardiomyopathies and skeletal myopathies.

pubmed

Tsikitis M, Diokmetzidou A, Liakopoulos P, Karipidou M, Kokkinopoulos I, Vatsellas G, Kloukina I, Kolovos P, Capetanaki Y.Cell Death Dis. 2025 Oct 16;16(1):723. doi: 10.1038/s41419-025-08056-3.