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.

The Impact of FBN1-α5β1 Axis in Fibro/Adipogenic Progenitor Cells (FAPCD9–) on Intramuscular Fat Content in Pigs

“…Intramuscular fat (IMF) deposition in pigs is regulated by multiple cell types, including endothelial cells, muscle cells, and pericytes. , In our study, scRNA-seq was employed to construct receptor–ligand libraries of different pig breeds during IMF deposition, enhancing our understanding of the adipogenic roles of various cellular populations. Additionally, we analyzed the heterogeneity of FAP to elucidate the mechanism behind the difference in IMF content between GDSS and YK.…”

“…23−25 Several studies have also documented the single-cell mapping of porcine skeletal muscle, 26,27 revealing the involvement of FAPs in intramuscular fat deposition. 27,28 However, FAPs exhibit heterogeneity, 29 focusing on the differences in the adipogenic mechanism of FAPs between fat-type and lean-type pigs.…”

“…Previously, intramuscular vascular stem cells (IVSC), composed of satellite cells, FAPs, immune cells, and endothelial cells, − have been isolated from skeletal muscle of newborn piglets and used in adipogenesis studies. ,, However, the precise cellular origin of intramuscular fat cells remains unclear. Recently, single-cell RNA sequencing (scRNA-seq) has elucidated the diversity of cell population in tissues, providing insights into the heterogeneity of gene expression across cells. , Studies based on scRNA-seq have effectively revealed the molecular mechanisms underlying adipogenic formation in distinct regions of adipose tissue. − Several studies have also documented the single-cell mapping of porcine skeletal muscle, , revealing the involvement of FAPs in intramuscular fat deposition. , However, FAPs exhibit heterogeneity, and as of now, the precise origin of IMF remains unclear. Moreover, there are few investigations focusing on the differences in the adipogenic mechanism of FAPs between fat-type and lean-type pigs.…”

Single-Cell RNA Sequencing Reveals the Cellular Landscape of Longissimus Dorsi in a Newborn Suhuai Pig

“…A study has unveiled the transcriptional profiles of over 200,000 porcine cells across 20 tissues (excluding muscle) in pigs through scRNA-seq [19]. Recently, a study disclosed the single-cell profiles of LD from three distinct pig breeds (Wild boars, Laiwu pigs, and Duroc pigs), unveiling variations in cell populations, communication signaling networks, and skeletal muscle expression profiles among three different pig breeds [6]. These studies reveal heterogeneity in the physiological properties of LD among different pig breeds.…”

“…The inherent cellular composition and physiological functions of meat endow its characteristics [4,5]. As a representative muscle model for assessing lean meat production and evaluating meat quality in pig breeding, the LD has been the focus of numerous studies, encompassing relevant data such as histological, genetic, transcriptomic, and epigenetic information [6,7].…”