Association Analysis of Single-Cell RNA Sequencing and Proteomics Reveals a Vital Role of Ca2+ Signaling in the Determination of Skeletal Muscle Development Potential
Kai Qiu, Doudou Xu, Liqi Wang, Xin Zhang, Ning Jiao, Lu Gong, Jingdong Yin
Abstract
This study is aimed at exploring the mechanism underlying the homeostasis between myogenesis and adipogenesis in skeletal muscle using a special porcine model with a distinct phenotype on muscle growth rate and intramuscular fat deposition. Differentiation potential of muscle-derived Myo-lineage cells of lean-type pigs was significantly enhanced relative to obese-type pigs, while that of their Adi-lineage cells was similar. Single-cell RNA sequencing revealed that lean-type pigs reserved a higher proportion of Myo-lineage cells in skeletal muscle relative to obese-type pigs. Besides, Myo-lineage cells of the lean-type pig settled closer to the original stage of muscle-derived progenitor cells. Proteomics analysis found that differentially expressed proteins between two sources of Myo-lineage cells are mainly involved in muscle development, cell proliferation and differentiation, ion homeostasis, apoptosis, and the MAPK signaling pathway. The regulation of intracellular ion homeostasis, Ca2+ in particular, significantly differed between two sources of Myo-lineage cells. Ca2+ concentration in both cytoplasm and endoplasmic reticulum was lower in Myo-lineage cells of lean-type pigs relative to obese-type pigs. In conclusion, a higher proportion and stronger differentiation capacity of Myo-lineage cells are the main causes for the higher capability of myogenic differentiation and lower intramuscular fat deposition. Relative low concentration of cellular Ca2+ is advantageous for Myo-lineage cells to keep a potent differentiation potential.