Zhu Zhaowei, Kuang Rui, Su Shouwen, Zhang Yujing, Wu Guanggeng, Zhang Yi, Pang Vincent, Zhou Xiang, Yang Yan, Li Ge, He Bo, Xu Yangbin
Department of Plastic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, China.
Orthopaedic Trauma and Joint Department, Department of Orthopedics, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510000, China.
Cell Mol Biol Lett. 2025 Oct 17;30(1):120. doi: 10.1186/s11658-025-00796-6.
Phenotypic transformation of Schwann cells (SCs) plays a crucial role in nerve regeneration. Previous studies have demonstrated that Runx2 significantly influences the biological behavior of SCs. Nonetheless, the regulatory mechanisms that govern its epigenetic regulation are not yet fully elucidated.
To facilitate this investigation, an adenovirus for the overexpression of Runx2 was constructed. Healthy adult Sprague-Dawley rats, weighing between 100 and 150 g and irrespective of sex, were randomly selected for the study. After establishing a model of sciatic nerve crush injury, tissue samples were harvested for histological analysis at both 4 and 7 days post-injury. In vitro, an Runx2-overexpressing SC line was established. Thorough analysis of transcriptome data, coupled with CUT&Tag sequencing of histones and transcription factors in SCs following Runx2 overexpression, was conducted. Additionally, single-cell RNA sequencing data from GSE216665 were incorporated to elucidate the mechanistic role of Runx2. The findings were subsequently validated through dual-luciferase assays.
Following nerve crush injury, Runx2-positive SCs were identified at the injury site. Through comprehensive multiomics analysis, we discovered that lipid metabolism was disrupted in Runx2-overexpressing SCs. Further investigation established a detailed super-silencer landscape in these cells, revealing that elevated Runx2 levels form a super-silencer within the transcriptional regulatory region of the Lpl gene, thereby downregulating Lpl expression.
Runx2 can modulate the biological behavior of SCs by forming super-silencers that interfere with the expression of lipid metabolism genes, such as Lpl, thereby altering the metabolic capacity of SCs.
雪旺细胞（SCs）的表型转化在神经再生中起关键作用。先前的研究表明，Runx2对SCs的生物学行为有显著影响。然而，其表观遗传调控的机制尚未完全阐明。
为便于此项研究，构建了用于过表达Runx2的腺病毒。随机选取体重100至150克、不分性别的健康成年Sprague-Dawley大鼠用于该研究。建立坐骨神经挤压伤模型后，在损伤后第4天和第7天采集组织样本进行组织学分析。在体外，建立了过表达Runx2的SCs细胞系。对转录组数据进行了全面分析，并对过表达Runx2后的SCs中的组蛋白和转录因子进行了CUT&Tag测序。此外，纳入了来自GSE216665的单细胞RNA测序数据以阐明Runx2的作用机制。随后通过双荧光素酶测定对结果进行了验证。
在神经挤压伤后，在损伤部位鉴定出Runx2阳性SCs。通过全面的多组学分析，我们发现过表达Runx2的SCs中脂质代谢受到破坏。进一步研究在这些细胞中建立了详细的超级沉默子图谱，揭示Runx2水平升高在Lpl基因的转录调控区域内形成超级沉默子，从而下调Lpl表达。
Runx2可通过形成干扰脂质代谢基因（如Lpl）表达的超级沉默子来调节SCs的生物学行为，从而改变SCs的代谢能力。
