Single-nucleus transcriptomics reveals functional compartmentalization in syncytial skeletal muscle cells.
Minchul KimVedran FrankeBettina BrandtElijah David LowensteinVerena SchöwelSimone SpulerAltuna AkalinCarmen BirchmeierPublished in: Nature communications (2020)
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/ ).
Keyphrases
- skeletal muscle
- single cell
- induced apoptosis
- insulin resistance
- cell cycle arrest
- mouse model
- ejection fraction
- electronic health record
- gene expression
- big data
- palliative care
- endoplasmic reticulum stress
- genome wide
- cell death
- prognostic factors
- newly diagnosed
- early onset
- heat shock
- pi k akt
- metabolic syndrome
- cell proliferation
- deep learning
- high resolution
- signaling pathway
- oxidative stress
- artificial intelligence
- adipose tissue
- wild type