Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China; Engineering Research Center of North-East Cold Region Beef Cattle Science & Technology Innovation, Ministry of Education, Department of Animal Science, Yanbian University, Yanji 133002, China.
Engineering Research Center of North-East Cold Region Beef Cattle Science & Technology Innovation, Ministry of Education, Department of Animal Science, Yanbian University, Yanji 133002, China.
Int J Biol Macromol. 2024 Aug;275(Pt 2):133639. doi: 10.1016/j.ijbiomac.2024.133639. Epub 2024 Jul 4.
Clarifying the cellular origin and regulatory mechanisms of intramuscular fat (IMF) deposition is crucial for improving beef quality. Here, we used single-nucleus RNA sequencing to analyze the structure and heterogeneity of skeletal muscle cell populations in different developmental stages of Yanbian cattle and identified eight cell types in two developmental stages of calves and adults. Among them, fibro/adipogenic progenitors (FAPs) expressing CD29 (ITGA7) and CD56 (NCAM1) surface markers were committed to IMF deposition in beef cattle and expressed major Wnt ligands and receptors. LY2090314/XAV-939 was used to activate/inhibit Wnt/β-catenin signal. The results showed that the blockade of Glycogen Synthase Kinase 3 (GSK3) by LY2090314 promoted the stabilization of β-catenin and reduced the expression of genes related adipogenic differentiation (e.g., PPARγ and C/EBPα) in bovine FAPs, confirming the anti-adipogenic effect of GSK3. XAV-939 inhibition of the Wnt/β-catenin pathway promoted the lipid accumulation capacity of FAPs. Furthermore, we found that blocking GSK3 enhanced the paracrine effects of FAPs-MuSCs and increased myotube formation in muscle satellite cells (MuSCs). Overall, our results outline a single-cell atlas of skeletal muscle development in Yanbian cattle, revealed the role of Wnt/GSK3/β-catenin signaling in FAPs adipogenesis, and provide a theoretical basis for further regulation of bovine IMF deposition.
阐明肌内脂肪（IMF）沉积的细胞起源和调控机制对于改善牛肉质量至关重要。在这里，我们使用单核 RNA 测序分析了不同发育阶段延边牛骨骼肌细胞群体的结构和异质性，并在小牛和成年的两个发育阶段鉴定了 8 种细胞类型。其中，表达 CD29（ITGA7）和 CD56（NCAM1）表面标志物的成纤维/脂肪祖细胞（FAPs）在肉牛中被认为是 IMF 沉积的关键，并且表达主要的 Wnt 配体和受体。LY2090314/XAV-939 被用于激活/抑制 Wnt/β-catenin 信号。结果表明，通过 LY2090314 阻断糖原合酶激酶 3（GSK3）促进了β-catenin 的稳定，并降低了牛 FAPs 中与脂肪分化相关的基因表达（例如，PPARγ 和 C/EBPα），证实了 GSK3 的抗脂肪生成作用。XAV-939 抑制 Wnt/β-catenin 通路促进了 FAPs 的脂质积累能力。此外，我们发现阻断 GSK3 增强了 FAPs-MuSCs 的旁分泌作用，并增加了肌肉卫星细胞（MuSCs）中的肌管形成。总体而言，我们的研究结果描绘了延边牛骨骼肌发育的单细胞图谱，揭示了 Wnt/GSK3/β-catenin 信号在 FAPs 脂肪生成中的作用，并为进一步调节牛 IMF 沉积提供了理论依据。
