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Decoding the transcriptome of Duchenne muscular dystrophy to the single nuclei level reveals clinical-genetic correlations

Lookup NU author(s): Esther Fernández-SimónORCiD, Patricia Pinol Jurado, Dr Elisa Villalobos VillegasORCiD, Dr Alexandra Monceau, Dr Marianela Schiava, Jose Verdú-DíazORCiD, James Clark, Zoe Laidler, Priyanka Mehra, Rasya Gokul Nath, Dr Chiara Marini Bettolo, Professor Giorgio TascaORCiD, Professor Volker StraubORCiD, Professor Michela GuglieriORCiD, Professor Jordi Diaz ManeraORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023, The Author(s).Duchenne muscular dystrophy is a genetic disease produced by mutations in the dystrophin gene characterized by early onset muscle weakness leading to severe and irreversible disability. The cellular and molecular consequences of the lack of dystrophin in humans are only partially known, which is crucial for the development of new therapies aiming to slow or stop the progression of the disease. Here we have analyzed quadriceps muscle biopsies of seven DMD patients aged 2 to 4 years old and five age and gender matched controls using single nuclei RNA sequencing (snRNAseq) and correlated the results obtained with clinical data. SnRNAseq identified significant differences in the proportion of cell population present in the muscle samples, including an increase in the number of regenerative fibers, satellite cells, and fibro-adipogenic progenitor cells (FAPs) and a decrease in the number of slow fibers and smooth muscle cells. Muscle samples from the younger patients with stable mild weakness were characterized by an increase in regenerative fibers, while older patients with moderate and progressive weakness were characterized by loss of muscle fibers and an increase in FAPs. An analysis of the gene expression profile in muscle fibers identified a strong regenerative signature in DMD samples characterized by the upregulation of genes involved in myogenesis and muscle hypertrophy. In the case of FAPs, we observed upregulation of genes involved in the extracellular matrix regeneration but also several signaling pathways. Indeed, further analysis of the potential intercellular communication profile showed a dysregulation of the communication profile in DMD samples identifying FAPs as a key regulator of cell signaling in DMD muscle samples. In conclusion, our study has identified significant differences at the cellular and molecular levels in the different cell populations present in skeletal muscle samples of patients with DMD compared to controls.

Publication metadata

Author(s): Suarez-Calvet X, Fernandez-Simon E, Natera D, Jou C, Pinol-Jurado P, Villalobos E, Ortez C, Monceau A, Schiava M, Codina A, Verdu-Diaz J, Clark J, Laidler Z, Mehra P, Gokul-Nath R, Alonso-Perez J, Marini-Bettolo C, Tasca G, Straub V, Guglieri M, Nascimento A, Diaz-Manera J

Publication type: Article

Publication status: Published

Journal: Cell Death and Disease

Year: 2023

Volume: 14

Issue: 9

Online publication date: 07/09/2023

Acceptance date: 22/08/2023

Date deposited: 29/09/2023

ISSN (electronic): 2041-4889

Publisher: Springer Nature


DOI: 10.1038/s41419-023-06103-5

PubMed id: 37673877


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Funder referenceFunder name
Academy of Medical Sciences Professorship Scheme
Fundación Isabel Gemio
La Marató de TV3
Medical Research Council