A single-cell atlas of bovine skeletal muscle reveals mechanisms regulating intramuscular adipogenesis and fibrogenesis

Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cachexia, sarcopenia and muscle sarcopenia and muscle, 2023-10, Vol.14 (5), p.2152-2167
Main Authors: Wang, Leshan, Gao, Peidong, Li, Chaoyang, Liu, Qianglin, Yao, Zeyang, Li, Yuxia, Zhang, Xujia, Sun, Jiangwen, Simintiras, Constantine, Welborn, Matthew, McMillin, Kenneth, Oprescu, Stephanie, Kuang, Shihuan, Fu, Xing
Format: Article
Language:English
Subjects:
Adipogenesis
Adipogenesis - physiology
Aged
Animals
Beef cattle
Blood vessels
Cattle
Cell Differentiation
Cells
Communication
Comparative analysis
Datasets
Fibro/adipogenic progenitor
Fibrogenesis
Gene expression
Genomics
Humans
Intramuscular adipose tissue
Mice
Muscle, Skeletal - metabolism
Muscular Dystrophy, Duchenne
Musculoskeletal system
Original
Reproducibility of Results
Single‐cell RNAseq
Smooth muscle
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis. Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell-cell communication analysis, were performed to elucidate heterogeneities and differentiation processes of individual cell types and differences between cattle breeds. Experiments were conducted to validate the function and specificity of identified key regulatory and marker genes. Integrated analysis with multiple published human and non-human primate datasets was performed to identify common mechanisms. A total of 32 708 cells and 21 clusters were identified, including fibro/adipogenic progenitor (FAP) and other resident and infiltrating cell types. We identified an endomysial adipogenic FAP subpopulation enriched for COL4A1 and CFD (log2FC = 3.19 and 1.92, respectively; P 
ISSN:2190-5991
2190-6009
DOI:10.1002/jcsm.13292