» Articles » PMID: 35646075

Heterogeneous Skeletal Muscle Cell and Nucleus Populations Identified by Single-Cell and Single-Nucleus Resolution Transcriptome Assays

Overview
Journal Front Genet
Date 2022 Jun 1
PMID 35646075
Authors
Affiliations
Soon will be listed here.
Abstract

Single-cell RNA-seq (scRNA-seq) has revolutionized modern genomics, but the large size of myotubes and myofibers has restricted use of scRNA-seq in skeletal muscle. For the study of muscle, single-nucleus RNA-seq (snRNA-seq) has emerged not only as an alternative to scRNA-seq, but as a novel method providing valuable insights into multinucleated cells such as myofibers. Nuclei within myofibers specialize at junctions with other cell types such as motor neurons. Nuclear heterogeneity plays important roles in certain diseases such as muscular dystrophies. We survey current methods of high-throughput single cell and subcellular resolution transcriptomics, including single-cell and single-nucleus RNA-seq and spatial transcriptomics, applied to satellite cells, myoblasts, myotubes and myofibers. We summarize the major myonuclei subtypes identified in homeostatic and regenerating tissue including those specific to fiber type or at junctions with other cell types. Disease-specific nucleus populations were found in two muscular dystrophies, FSHD and Duchenne muscular dystrophy, demonstrating the importance of performing transcriptome studies at the single nucleus level in muscle.

Citing Articles

LMNA R482L mutation causes impairments in C2C12 myoblasts subpopulations, alterations in metabolic reprogramming during differentiation, and oxidative stress.

Ivanova O, Predeus A, Sorokina M, Ignatieva E, Bobkov D, Sukhareva K Sci Rep. 2025; 15(1):5358.

PMID: 39948343 PMC: 11825939. DOI: 10.1038/s41598-025-88219-6.


Cytokine expression and cytokine-mediated cell-cell communication during skeletal muscle regeneration revealed by integrative analysis of single-cell RNA sequencing data.

Barai P, Chen J J Cell Commun Signal. 2024; 18(4):e12055.

PMID: 39691872 PMC: 11647049. DOI: 10.1002/ccs3.12055.


The ENCODE mouse postnatal developmental time course identifies regulatory programs of cell types and cell states.

Rebboah E, Rezaie N, Williams B, Weimer A, Shi M, Yang X bioRxiv. 2024; .

PMID: 38915583 PMC: 11195270. DOI: 10.1101/2024.06.12.598567.


Single-nucleus RNA sequencing and lipidomics reveal characteristics of transcriptional and lipid composition in porcine longissimus dorsi muscle.

Yi L, Li Q, Zhu J, Cheng W, Xie Y, Huang Y BMC Genomics. 2024; 25(1):622.

PMID: 38902599 PMC: 11188186. DOI: 10.1186/s12864-024-10488-8.


Single-cell spatial transcriptomics reveals a dystrophic trajectory following a developmental bifurcation of myoblast cell fates in facioscapulohumeral muscular dystrophy.

Chen L, Kong X, Johnston K, Mortazavi A, Holmes T, Tan Z Genome Res. 2024; 34(5):665-679.

PMID: 38777608 PMC: 11216401. DOI: 10.1101/gr.278717.123.


References
1.
Lake B, Codeluppi S, Yung Y, Gao D, Chun J, Kharchenko P . A comparative strategy for single-nucleus and single-cell transcriptomes confirms accuracy in predicted cell-type expression from nuclear RNA. Sci Rep. 2017; 7(1):6031. PMC: 5519641. DOI: 10.1038/s41598-017-04426-w. View

2.
DellOrso S, Juan A, Ko K, Naz F, Perovanovic J, Gutierrez-Cruz G . Single cell analysis of adult mouse skeletal muscle stem cells in homeostatic and regenerative conditions. Development. 2019; 146(12). PMC: 6602351. DOI: 10.1242/dev.174177. View

3.
Zeng W, Jiang S, Kong X, El-Ali N, Ball Jr A, Ma C . Single-nucleus RNA-seq of differentiating human myoblasts reveals the extent of fate heterogeneity. Nucleic Acids Res. 2016; 44(21):e158. PMC: 5137429. DOI: 10.1093/nar/gkw739. View

4.
Chemello F, Wang Z, Li H, McAnally J, Liu N, Bassel-Duby R . Degenerative and regenerative pathways underlying Duchenne muscular dystrophy revealed by single-nucleus RNA sequencing. Proc Natl Acad Sci U S A. 2020; 117(47):29691-29701. PMC: 7703557. DOI: 10.1073/pnas.2018391117. View

5.
Grosselin K, Durand A, Marsolier J, Poitou A, Marangoni E, Nemati F . High-throughput single-cell ChIP-seq identifies heterogeneity of chromatin states in breast cancer. Nat Genet. 2019; 51(6):1060-1066. DOI: 10.1038/s41588-019-0424-9. View