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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1569296
This article is part of the Research TopicRegulation of intervertebral disc homeostasis and the pathological or pathophysiological alterations under various harmful stimuli during aging processView all 5 articles
Single-Cell RNA-Seq uncovers lineage-specific regulatory alterations of fibroblasts and endothelial cells in ligamentum flavum hypertrophy
Provisionally accepted- Nanjing Jiangning Hospital, Nanjing, China
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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.
Keywords: Lumbar spinal stenosis, Hypertrophy, ScRNA-seq, fibroblast, endothelial cell, Ligamentum Flavum
Received: 31 Jan 2025; Accepted: 21 Apr 2025.
Copyright: © 2025 Chen, Zhang, Feng, Ma and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chao Sun, Nanjing Jiangning Hospital, Nanjing, China
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