Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Muscle Samples
2.2. RNA Preparation from Muscle Tissue
2.3. RNA-Seq Analysis
2.4. Single-Nucleus RNA Sequencing
2.5. Bioinformatics Analysis
2.6. Immunostaining Analysis
2.7. Tissue Staining
3. Results
3.1. Comparison of Gene Expression in Different Muscle Tissues
3.2. Comparison of Cells Using Single-Nucleus RNA-Seq Analysis
4. Discussion
4.1. Muscle Tissue Composition
4.2. Lipid Metabolism and Lipoxygenase
4.3. Collagen and Remodeling
4.4. Fibro–Adipogenic Progenitor Heterogeneity
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
IMF | Intramuscular fat |
scRNA-seq | Single-cell RNA sequencing |
snRNA-seq | Single-nucleus RNA sequencing |
NGS | Next-generation sequencing |
RIN | RNA integrity |
DEG | Differentially expressed gene |
TPM | Transcripts per million |
GO | Gene Ontology |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
SE | Standard error |
NS | Not significant |
UMAP | Uniform manifold approximation and projection |
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Muscle Tissue | Total Read (Count) | Mapped Read (Count) | Mapped Read (%) |
---|---|---|---|
Neck | 70,838,677 | 70,609,753 | 99.7 |
Round | 76,025,869 | 75,783,954 | 99.7 |
Brisket | 70,529,128 | 70,263,281 | 99.6 |
Muscle Tissue | Estimated Number of Cells | Median Genes Per Cell | Reads Mapped to Genome (%) | Total Genes Detected |
---|---|---|---|---|
Brisket | 38,939 | 1654 | 97.10% | 25,580 |
Round | 51,506 | 1573 | 96.80% | 25,955 |
Cell Type | Marker Gene |
---|---|
Myofibers | Nitric oxide synthase 1 (NOS1) |
Transforming acidic coiled-coil-containing protein 2 (TACC2) | |
Myosin heavy chain 1 (MYH1) | |
Myosin heavy chain 2 (MYH2) | |
Myosin heavy chain 7 (MYH7) | |
Fibro–adipogenic progenitors (FAPs) | Platelet-derived growth factor receptor alpha (PDGFRA) |
Tenocytes | Cartilage oligomeric matrix protein (COMP) |
Mohawk homeobox (MKX) | |
Chwann cells | Neural cell adhesion molecule 1 (NCAM1) |
Immune cells | Protein tyrosine phosphatase receptor type C (PTPRC) |
Myogenic cells (muscle satellite cells) | Myogenic factor 5 (MYF5) |
Smooth muscle cells | Actin alpha 2 (ACTA2) |
Endothelial cells | Platelet and endothelial cell adhesion molecule 1 (PECAM1) |
Adipocytes | Adiponectin (ADIPOQ) |
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Ueda, S.; Kitamura, C.; Tateoka, Y.; Kanai, A.; Suzuki, Y.; Fukuda, I.; Shirai, Y. Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation. Metabolites 2025, 15, 231. https://doi.org/10.3390/metabo15040231
Ueda S, Kitamura C, Tateoka Y, Kanai A, Suzuki Y, Fukuda I, Shirai Y. Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation. Metabolites. 2025; 15(4):231. https://doi.org/10.3390/metabo15040231
Chicago/Turabian StyleUeda, Shuji, Chiaki Kitamura, Yuka Tateoka, Akinori Kanai, Yutaka Suzuki, Itsuko Fukuda, and Yasuhito Shirai. 2025. "Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation" Metabolites 15, no. 4: 231. https://doi.org/10.3390/metabo15040231
APA StyleUeda, S., Kitamura, C., Tateoka, Y., Kanai, A., Suzuki, Y., Fukuda, I., & Shirai, Y. (2025). Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation. Metabolites, 15(4), 231. https://doi.org/10.3390/metabo15040231