Chen Yongxin, Zhang Jue, Feng Xincheng, Ma Qinghong, Sun Chao
Department of Spine Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Front Immunol. 2025 May 15;16:1569296. doi: 10.3389/fimmu.2025.1569296. eCollection 2025.
Lumbar spinal stenosis (LSS) represents a major global healthcare burden resulting in back pain and disorders of the limbs among the elderly population. The hypertrophy of ligamentum flavum (HLF), marked by fibrosis and inflammation, significantly contributes to LSS. Fibroblasts and endothelial cells are two important cells in the pathological process of ligamentum flavum (LF) fibrosis and inflammation. These two cells exhibit heterogeneity in various fibrotic diseases, yet their heterogeneity in LF fibrosis remains poorly defined.
Using single-cell RNA-seq, we examined the alterations of fibroblasts, endothelial cells, and key genes in the hypertrophic LF, aiming to establish a comprehensive single-cell atlas of LF to identify high-priority targets for pharmaceutical treatment of LSS.
Here, we find there are five distinct subpopulations of LF fibroblasts: secretory-papillary, secretory-reticular, mesenchymal, pro-inflammatory, and unknown. Importantly, in HLF, the proportion of mesenchymal fibroblast subpopulations increases significantly compared to normal LF (NLF), reflecting their close association with the pathogenesis of HLF. Furthermore, critical target genes that might be involved in HLF and fibrosis, such as MGP, ASPN, OGN, LUM, and CTSK, are identified. In addition, we also investigate the heterogeneity of endothelial cells and highlight the critical role of AECs subpopulation in LF fibrosis.
This study will contribute to our understanding of the pathogenesis of HLF and offer possible targets for the treatment of fibrotic diseases.
腰椎管狭窄症（LSS）是一项重大的全球医疗负担，导致老年人群出现背痛和肢体功能障碍。以纤维化和炎症为特征的黄韧带肥厚（HLF）是导致LSS的重要原因。成纤维细胞和内皮细胞是黄韧带（LF）纤维化和炎症病理过程中的两种重要细胞。这两种细胞在各种纤维化疾病中表现出异质性，但它们在LF纤维化中的异质性仍未明确。
我们使用单细胞RNA测序技术，研究了肥厚性LF中成纤维细胞、内皮细胞和关键基因的变化，旨在建立LF的综合单细胞图谱，以确定LSS药物治疗的高优先级靶点。
在此，我们发现LF成纤维细胞有五个不同的亚群：分泌性乳头亚群、分泌性网状亚群、间充质亚群、促炎亚群和未知亚群。重要的是，与正常LF（NLF）相比，HLF中间充质成纤维细胞亚群的比例显著增加，这反映了它们与HLF发病机制的密切关系。此外，还确定了可能参与HLF和纤维化的关键靶基因，如MGP、ASPN、OGN、LUM和CTSK。此外，我们还研究了内皮细胞的异质性，并强调了AECs亚群在LF纤维化中的关键作用。
本研究将有助于我们理解HLF的发病机制，并为纤维化疾病的治疗提供可能的靶点。
