Single-nucleus transcriptomics reveals functional compartmentalization in syncytial skeletal muscle cells

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Item Type:

Article

Title:

Single-nucleus transcriptomics reveals functional compartmentalization in syncytial skeletal muscle cells

Creators Name:

Kim, M. and Franke, V. and Brandt, B. and Lowenstein, E.D. and Schöwel, V. and Spuler, S. and Akalin, A. and Birchmeier, C.

Abstract:

Syncytial skeletal muscle cells contain hundreds of nuclei in a shared cytoplasm. We investigated nuclear heterogeneity and transcriptional dynamics in the uninjured and regenerating muscle using single-nucleus RNA-sequencing (snRNAseq) of isolated nuclei from muscle fibers. This revealed distinct nuclear subtypes unrelated to fiber type diversity, previously unknown subtypes as well as the expected ones at the neuromuscular and myotendinous junctions. In fibers of the Mdx dystrophy mouse model, distinct subtypes emerged, among them nuclei expressing a repair signature that were also abundant in the muscle of dystrophy patients, and a nuclear population associated with necrotic fibers. Finally, modifications of our approach revealed the compartmentalization in the rare and specialized muscle spindle. Our data identifies nuclear compartments of the myofiber and defines a molecular roadmap for their functional analyses; the data can be freely explored on the MyoExplorer server (https://shiny.mdc-berlin.de/MyoExplorer/).

Keywords:

Animal Disease Models, Cell Line, Cell Nucleus, Cytoplasm, Developmental Gene Expression Regulation, Genetic Heterogeneity, Inbred mdx Mice, Muscular Dystrophies, RNA-Seq, Regeneration, Skeletal Muscle, Skeletal Muscle Fibers, Tendons, Transcriptome, Animals, Mice

Source:

Nature Communications

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Volume:

Page Range:

6375

Date:

11 December 2020

Official Publication: