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Single-Cell RNA-Sequencing Provides Insight into Skeletal Muscle Evolution during the Selection of Muscle Characteristics.

ABSTRACT: Skeletal muscle comprises a large, heterogeneous assortment of cell populations that interact to maintain muscle homeostasis, but little is known about the mechanism that controls myogenic development in response to artificial selection. Different pig (Sus scrofa) breeds exhibit distinct muscle phenotypes resulting from domestication and selective breeding. Using unbiased single-cell transcriptomic sequencing analysis (scRNA-seq), the impact of artificial selection on cell profiles is investigated in neonatal skeletal muscle of pigs. This work provides panoramic muscle-resident cell profiles and identifies novel and breed-specific cells, mapping them on pseudotime trajectories. Artificial selection has elicited significant changes in muscle-resident cell profiles, while conserving signs of generational environmental challenges. These results suggest that fibro-adipogenic progenitors serve as a cellular interaction hub and that specific transcription factors identified here may serve as candidate target regulons for the pursuit of a specific muscle phenotype. Furthermore, a cross-species comparison of humans, mice, and pigs illustrates the conservation and divergence of mammalian muscle ontology. The findings of this study reveal shifts in cellular heterogeneity, novel cell subpopulations, and their interactions that may greatly facilitate the understanding of the mechanism underlying divergent muscle phenotypes arising from artificial selection.

SUBMITTER: Xu D

PROVIDER: S-EPMC10724408 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Single-Cell RNA-Sequencing Provides Insight into Skeletal Muscle Evolution during the Selection of Muscle Characteristics.

Xu Doudou D Wan Boyang B Qiu Kai K Wang Yubo Y Zhang Xin X Jiao Ning N Yan Enfa E Wu Jiangwei J Yu Run R Gao Shuai S Du Min M Liu Chousheng C Li Mingzhou M Fan Guoping G Yin Jingdong J

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20231023 35

Skeletal muscle comprises a large, heterogeneous assortment of cell populations that interact to maintain muscle homeostasis, but little is known about the mechanism that controls myogenic development in response to artificial selection. Different pig (Sus scrofa) breeds exhibit distinct muscle phenotypes resulting from domestication and selective breeding. Using unbiased single-cell transcriptomic sequencing analysis (scRNA-seq), the impact of artificial selection on cell profiles is investigat ...[more]

PMID: 37870215

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Project description:BackgroundAgeing is accompanied by sarcopenia and intramuscular fat (IMAT) infiltration. In skeletal muscle, fat infiltration is a common feature in several myopathies and is associated with muscular dysfunction and insulin resistance. However, the cellular origin and lipidomic and transcriptomic changes during fat infiltration in skeletal muscle remain unclear.MethodsIn the current study, we generated a high IMAT-infiltrated skeletal muscle model by glycerol (GLY) injection. Single-cell RNA sequencing and lineage tracing were performed on GLY-injured skeletal muscle at 5 days post-injection (DPI) to identify the cell origins and dynamics. Lipidomics and RNA sequencing were performed on IMAT-infiltrated skeletal muscle at 14 DPI (or 17 DPI for the cold treatment) to analyse alterations of lipid compositions and gene expression levels.ResultsWe identified nine distinct major clusters including myeloid-derived cells (52.13%), fibroblast/fibro/adipogenic progenitors (FAPs) (23.24%), and skeletal muscle stem cells (2.02%) in GLY-injured skeletal muscle. Clustering and pseudotemporal trajectories revealed six subpopulations in fibroblast/FAPs and 10 subclusters in myeloid-derived cells. A subpopulation of myeloid-derived cells expressing adipocyte-enriched genes and Pdgfra- /Cd68+ cells displayed lipid droplets upon adipogenic induction, indicating their adipogenic potential. Lipidomic analysis revealed the changes of overall lipid classes composition (e.g. triglycerides (TAGs) increased by 19.3 times, P = 0.0098; sulfoquinovosyl diacylglycerol decreased by 83%, P = 0.0056) and in the distribution of lipids [e.g. TAGs (18:2/18:2/22:6) increased by 181.6 times, P = 0.021] between GLY-group and saline control. RNA-seq revealed 1847 up-regulated genes and 321 down-regulated genes and significant changes in lipid metabolism-related pathways (e.g. glycerolipid pathway and glycerophospholipid pathway) in our model of GLY-injured skeletal muscle. Notably, short-term cold exposure altered fatty acid composition (e.g. saturated fatty acid decreased by 6.4%, P = 0.058) in fat-infiltrated muscles through directly affecting lipid metabolism pathways including PI3K-AKT and MAPK signalling pathway.ConclusionsOur results showed that a subpopulation of myeloid-derived cells may contribute to IMAT infiltration. GLY-induced IMAT infiltration changed the lipid composition and gene expression profiles. Short-term cold exposure might regulate lipid metabolism and its related signalling pathways in fat-infiltrated muscle. Our study provides a comprehensive resource describing the molecular signature of fat infiltration in skeletal muscle.

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Single-Cell RNA-Sequencing Provides Insight into Skeletal Muscle Evolution during the Selection of Muscle Characteristics.

Publications

Single-Cell RNA-Sequencing Provides Insight into Skeletal Muscle Evolution during the Selection of Muscle Characteristics.

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