Biology subjects

Gummert, J.

Publications and source records attributed to Gummert, J..

3 recordsLinked to original sources

bioRxiv2026

The DES-p.A120P mutation associated with biventricular arrhythmogenic cardiomyopathy has a dominant-negative effect on desmin filament assembly

Desmin is a muscle-specific intermediate filament protein, which connects different cell organelles and is highly relevant for the structural integrity of cardiomyocytes. Mutations in the DES gene, cause different cardiomyopathies including arrhythmogenic cardiomyopathy. In this study, we functionally investigate the novel genetic variant DES-p.A120P using cell transfection experiments including cardiomyocytes derived from induced pluripotent stem cells in combination with confocal microscopy. These experiments reveal that the filament assembly of desmin-p.A120P is disturbed - even when co-expressed with wild-type desmin. In conclusion, the functional characterization of desmin-p.A120P supports the classification as a pathogenic variant associated with arrhythmogenic cardiomyopathy.

genetics↗

bioRxiv2023

Atlas of DES (desmin) variants: Impact of variants located within the head domain on filament assembly

Desmin is a muscle-specific intermediate filament protein, which plays a significant role in providing structural integrity of cardiomyocytes by connecting different cell organelles and multi-protein complexes. DES mutations cause cardiomyopathies and skeletal myopathies. Most of these pathogenic mutations are localized in the highly conserved rod domain and affect the filament assembly. However, the impact of DES variants within the N-terminal head domain on the filament assembly process is widely unknown. Therefore, we inserted a set of 85 different head domain variants with unknown significance from human genetic databases in expression constructs and investigated their impact on filament formation in cell culture in combination with confocal microscopy. The majority of these desmin variants do not affect the filament assembly. However, the desmin variants -p.S13P, -p.N107D, -p.E108G and -p.K109E significantly inhibit the filament assembly. Additionally, we expressed and purified recombinant desmin and investigated the filament assembly defects by atomic force microscopy verifying these findings at the single molecular level. Furthermore, we truncated systematically the head domain to investigate which general parts of this domain are necessary for filament assembly. In summary, our functional investigations might be relevant for the classification of novel DES variants and the genetic counselling of patients carrying desmin head variants.

cell biology↗

bioRxiv2019

Identification of a human adult cardiac stem cell population with neural crest origin

Cardiovascular diseases are the major cause of death worldwide, emphasizing the necessity to better understand adult human cardiac cell biology and development. Although the adult heart was considered as a terminally differentiated organ, rare populations of cardiac stem cells (CSCs) have been described so far, with their developmental origin and endogenous function still being a matter of debate.\n\nHere, we identified a Nestin+/S100+/CD105+/Sca1+/cKit- population of CSCs in the myocardium of the adult human heart auricle. Isolated cells showed expression of characteristic neural crest-derived stem cell (NCSC) markers and kept their genetic stability during cultivation in vitro. Cultivated hCSCs efficiently gave rise to functional, beating cardiomyocytes, osteoblasts, adipocytes and neurons. Global transcriptome analysis via RNAseq showed a high similarity between the expression profiles of Nestin+/S100+/CD105+/Sca1+/cKit- hCSCs and adult human NCSCs from the nasal cavity (inferior turbinate stem cells, ITSCs). In detail, 88.1 % of all genes were significantly expressed in both stem cell populations particularly including common NCSC-markers. Based on these observations, we suggest a similar developmental origin of both stem cell populations.\n\nIn summary, we identified a human adult cardiac stem cell population with neural crest-origin, which may also contribute to endogenous cardiac tissue homeostasis and tissue repair in vivo.

cell biology↗