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The hypertrophy of the ligamentum flavum is assosciated with activation of the unfolded protein respone

ABSTRACT: The hypertrophy of the ligamentum flavum is assosciated with activation of the unfolded protein respone

PROVIDER: PRJNA450431 | ENA |

REPOSITORIES: ENA

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Single-Cell RNA-Seq uncovers lineage-specific regulatory alterations of fibroblasts and endothelial cells in ligamentum flavum hypertrophy

Project description: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.

2025-05-01 | GSE294458 | GEO

Changes in gene expression profile caused by mechanical stress in the ligamentum flavum -long term rabbit model-

Project description:To identify the changes in gene expression profile caused by mechanical stress in the ligamentum flavum, we performed resection of the L3-4 supraspinal muscle and L2-3, L4-5 posterolateral fusion with instrumentation to concentrate the mechanical stress with segmental instability at the L3-4 level. The control group underwent only surgical exposure as a sham operation. Both groups of rabbits were sacrificed at 1 year after surgery and total RNA were extracted from ligamentum flavum.

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Changes in gene expression profile caused by mechanical stress in the ligamentum flavum -short term rabbit model-

Project description:To identify the changes in gene expression profile caused by mechanical stress in the ligamentum flavum, we performed resection of the L3-4 supraspinal muscle and L2-3, L4-5 posterolateral fusion with instrumentation to concentrate the mechanical stress with segmental instability at the L3-4 level. The control group underwent only surgical exposure as a sham operation. Both groups of rabbits were sacrificed at 16 weeks after surgery and total RNA were extracted from ligamentum flavum.

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Single-cell analysis reveals fibroblast heterogeneity and myofibroblast conversion in ligamentum flavum hypertrophy

Project description:The ligamentum flavum (LF) is a crucial structure in maintaining spinal stability; however, hypertrophy of the LF is a significant contributor to lumbar spinal canal stenosis (LSCS). However, the mechanisms linking LF hypertrophy to the exacerbation of LSCS remain incompletely understood. In this study, we investigated the cellular proportions and signaling pathways observed in the hypertrophied LF using single-cell RNA sequencing (scRNA-seq). The LF tissues were obtained from three patients undergoing decompressive surgery at the lumbar level. These patients had been diagnosed with LSCS prior to surgery and had an LF thickness exceeding 4 mm. After single-cell dissociation of the LF tissues, scRNA-seq was performed. Fibroblasts accounted for 75% of the total cells, followed by endothelial cells, T cells, macrophages, and B cells. Among heterogeneous types of fibroblasts, we identified that a subset of fibroblasts trans-differentiated into myofibroblasts. Two types of macrophages that exhibited phenotypic plasticity akin to M1 and M2 states were observed. We also identified novel signaling pathways involved in fibroblast and immune cell interaction in the hypertrophied LF, such as GAS and GRN, as well as known signaling pathways, such as TGF-β, PDGF, CXCL, and ANGPTL. Our study highlights the transdifferentiation process from fibroblasts to myofibroblasts in the hypertrophied LF through intrinsic changes in and extrinsic influences of fibroblasts.

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Single-cell analysis reveals fibroblast heterogeneity and myofibroblast conversion in ligamentum flavum hypertrophy

Project description:Single-cell analysis reveals fibroblast heterogeneity and myofibroblast conversion in ligamentum flavum hypertrophy

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Single-Cell RNA-Seq uncovers lineage-specific regulatory alterations of fibroblasts and endothelial cells in ligamentum flavum hypertrophy

Project description:Single-Cell RNA-Seq uncovers lineage-specific regulatory alterations of fibroblasts and endothelial cells in ligamentum flavum hypertrophy

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The hypertrophy of the ligamentum flavum is assosciated with activation of the unfolded protein respone

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