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单细胞 RNA 测序和蛋白质组学的关联分析揭示了 Ca 信号在决定骨骼肌发育潜力中的重要作用。

Association Analysis of Single-Cell RNA Sequencing and Proteomics Reveals a Vital Role of Ca Signaling in the Determination of Skeletal Muscle Development Potential.

机构信息

College of Animal Science and Technology, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China.

College of Biological Sciences, China Agricultural University, Beijing 100193, China.

出版信息

Cells. 2020 Apr 22;9(4):1045. doi: 10.3390/cells9041045.

DOI:10.3390/cells9041045
PMID:32331484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7225978/
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, Ca in particular, significantly differed between two sources of Myo-lineage cells. Ca 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 Ca is advantageous for Myo-lineage cells to keep a potent differentiation potential.

摘要

本研究旨在利用一种具有独特表型的特殊猪模型,探索骨骼肌中肌生成和脂肪生成之间的平衡机制,该模型在肌肉生长速度和肌内脂肪沉积方面存在明显差异。与肥胖型猪相比,瘦型猪的肌肉源性 Myo 细胞系的分化潜力显著增强,而其 Adi 细胞系的分化潜力则相似。单细胞 RNA 测序显示,瘦型猪骨骼肌中 Myo 细胞系的比例高于肥胖型猪。此外,瘦型猪的 Myo 细胞系更接近肌肉源性祖细胞的原始阶段。蛋白质组学分析发现,两种来源的 Myo 细胞系之间差异表达的蛋白质主要参与肌肉发育、细胞增殖和分化、离子稳态、细胞凋亡和 MAPK 信号通路。两种 Myo 细胞系之间细胞内离子稳态的调节,特别是 Ca 的调节,存在显著差异。瘦型猪 Myo 细胞系的细胞质和内质网中的 Ca 浓度均低于肥胖型猪。总之,较高比例和较强分化能力的 Myo 细胞系是肌生成分化能力较高和肌内脂肪沉积较低的主要原因。相对较低的细胞内 Ca 浓度有利于 Myo 细胞系保持强大的分化潜能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/251e81012bbe/cells-09-01045-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/59897fd80ac0/cells-09-01045-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/d108e358ae4f/cells-09-01045-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/04070b136e02/cells-09-01045-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/c987e7fed28d/cells-09-01045-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/1da1af9929dd/cells-09-01045-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/6c5bcbc7d8cc/cells-09-01045-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/251e81012bbe/cells-09-01045-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/59897fd80ac0/cells-09-01045-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/d108e358ae4f/cells-09-01045-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/04070b136e02/cells-09-01045-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/c987e7fed28d/cells-09-01045-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/1da1af9929dd/cells-09-01045-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/6c5bcbc7d8cc/cells-09-01045-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e7/7225978/251e81012bbe/cells-09-01045-g007.jpg

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