猪肌肉卫星细胞和肌母细胞在成肌过程中的单细胞转录谱分析

Xu-dong Yi, He Yu, Rui Li, Tian-tian Zhao, Zhao-zhao He, Wei-jun Pang
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摘要

在这里,我们揭示了猪肌肉成肌的转录机制,这是猪肉生产的一个重要方面。通过对 3 日龄仔猪的背阔肌(LD)进行单细胞 RNA 测序,我们从 14,002 个细胞中划分出了 5 种主要细胞类型--肌肉细胞、纤维脂肪生成祖细胞、壁细胞、内皮细胞和免疫细胞。在肌肉细胞群中,我们特别发现了肌肉卫星细胞和肌母细胞,并通过 5388 个差异表达基因区分了这些细胞群。此外,我们的研究还发现了猪肌肉卫星细胞的新型细胞表面标志物,即 ITGA7、SDC2 和 SDC4。此外,我们还发现了 55 个转录因子,包括 AHCTF1、CEBPD 和 MAX,它们有助于调节肌肉的发育。通过预测性受体配体分析,我们发现了 16 个影响猪骨骼肌发育的分泌因子及其相关的细胞通讯通道。值得注意的是,我们发现分泌因子 ANGPTL4 是猪肌肉卫星细胞增殖和分化的抑制剂,并通过体外处理细胞系证实了其功能。我们认为 ANGTPL4 是治疗肌病的潜在靶点。总之,我们的研究结果有助于鉴定和描述肌生成基因和调控网络,从而加深我们对猪肌肉卫星细胞肌生成的了解,并为优化猪肉生产提供潜在的途径。
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Single-cell transcriptional profiling of porcine muscle satellite cells and myoblasts during myogenesis

Here, we unravel the transcriptional mechanisms that govern porcine muscle myogenesis, a crucial aspect of pork production. Through single cell RNA-sequencing of longissimus dorsi (LD) muscle from 3-day-old piglets, we delineated 5 major cell types from 14,002 cells—muscle cells, fibro-adipogenic progenitors, mural cells, endothelial cells, and immune cells. Within the muscle cell clusters, we specifically identified muscle satellite cells and myoblasts, with 5,388 differentially expressed genes distinguishing the cell populations. Furthermore, our investigation led to the identification of novel cell surface markers for porcine muscle satellite cells, namely ITGA7, SDC2, and SDC4. In addition, we found 55 transcription factors, including AHCTF1, CEBPD, and MAX, which contribute to the regulation of muscle development. Through predictive receptor–ligand analysis, we uncovered 16 secretory factors with associated cellular communication channels influencing porcine skeletal muscle development. Notably, we identified the secretory factor ANGPTL4 as an inhibitor of porcine muscle satellite cell proliferation and differentiation, and confirmed its function through the in vitro treatment of cell lines. We propose that ANGTPL4 is a potential target for the treatment of myopathy. Taken together, our findings contribute to the identification and characterization of myogenic genes and regulatory networks, which enhances our understanding of porcine muscle satellite cell myogenesis and offers potential avenues for optimizing pork production.

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