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A multidimensional single-cell approach to understand muscle dystrophy

Research Project
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01.01.2020
 - 31.12.2022

Duchenne Muscular Dystrophy (DMD) and LAMA2-related Muscular Dystrophy (LAMA2 MD) are devastating rare genetic diseases of childhood manifested by progressive skeletal muscle wasting and ultimately death. In both diseases, the muscle undergoes constant cycles of degeneration-regeneration exacerbated by intrinsic muscle stem cell (MuSC) dysfunction and their impaired ability to support long-term regeneration. Till date, the nature of the cellular changes that contribute to muscle pathologies are unknown. Specifically, there is critical lack of research that provides an unbiased elucidation of the cellular events underlying the different steps of muscle disease progression at the single-cell level. This impedes development of therapeutic strategies that can effectively treat these devastating diseases. Currently, there is no known cure for LAMA2 MD and no therapy that can halt DMD disease progression. The overall goal of our project is to use a combination of single-cell transcriptomics (RNA-sequencing) and proteomics (mass cytometry, CyTOF) to define the cellular composition of diseased muscle tissues at the single-cell resolution. We will delineate the different cell populations that pre-exist and arise during disease progression and classify the novel cellular subsets involved in this process. This data, in combination with genetic lineage tracing will allow reconstruction of the MuSC lineage hierarchy. We will further characterize cellular subpopulations associated with human muscle dystrophies by performing 3-Dimensional intact-tissue RNA sequencing on patient biopsies. Thus, MYOCITY will significantly advance the current understanding of muscle dystrophies, uncover disease-related subsets in human biopsies and also develop new biomarkers and eventually new pharmacological approaches that will stimulate intrinsic muscle tissue repair.

Collaborations & Cooperations

2023 - Participation or Organization of Collaborations on an international level
Le Grand, Fabien, Professor, Institut National pour la Santé et la Recherche Médicale (INSERM), Research cooperation
2023 - Participation or Organization of Collaborations on an international level
Previtali, Stefano, Professor, IRCCS Ospedale San Raffaele, Milano, Research cooperation
2023 - Participation or Organization of Collaborations on an international level
Rudnicki, Michael, Professor, University of Ottawa, Research cooperation

Funding

A multidimensional single-cell approach to understand muscle dystrophy

Weitere Europäische Forschungsprojekte (Eurostars, ESF, Interreg etc.) (GrantsTool), 01.2020-12.2022 (36)
PI : Rüegg, Markus A..

Members (1)

Profile Photo

Markus A. Rüegg

Principal Investigator