2. Academic Validation
  3. GSK3 regulation Wnt/β-catenin signaling affects adipogenesis in bovine skeletal muscle fibro/adipogenic progenitors

GSK3 regulation Wnt/β-catenin signaling affects adipogenesis in bovine skeletal muscle fibro/adipogenic progenitors

  • Int J Biol Macromol. 2024 Jul 4;275(Pt 2):133639. doi: 10.1016/j.ijbiomac.2024.133639.
Junfang Zhang 1,  Enze Wang 2,  Qiang Li 2,  Yinghua Peng 3,  Huaina Jin 2,  Sajida Naseem 2,  Bin Sun 2,  Sungkwon Park 4,  Seongho Choi 5,  Xiangzi Li 6
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China.
  • 4 Department of Food Science and Biotechnology, Sejong University, Seoul 05006, Republic of Korea.
  • 5 Department of Animal Science, Chungbuk National University, Cheongju 28644, Republic of Korea.
  • 6 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. Electronic address: lxz@ybu.edu.cn.
PMID: 38969042 DOI: 10.1016/j.ijbiomac.2024.133639
Abstract

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)pos and CD56 (NCAM1)neg 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.

Keywords

Fibro/adipogenic progenitor; Glycogen synthase kinase 3; Intramuscular fat; Single-nucleus RNA-sequencing; Wnt/β-catenin signaling.

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