Evidence map›Paper›PMID 40001138›Full record

ArticleBiomarker research2025

Single-cell multi-omics analysis identifies SPP1

Chengshuo Fei, Yanlin Chen, Ruiqian Tan, Xinxing Yang, Guanda Wu, Chenglong Li, Jiawei Shi, Shiyong Le, Wenjie Yang, Jiajia Xu and 2 more

Abstract read
In one paragraph

Article in Biomarker research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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  7. Multifaceted regulation of immune cells in radiation-induced pulmonary fibrosis: from mechanistic insights to targeted therapies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. The pro-fibrogenic role of SPP1Frontiers in immunology · 2026
    Review
  14. Review
  15. Review
  16. Article
  17. Biological mechanisms underlying the ossification of ligamentum flavum and potential therapeutic targets derived from current research.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2025
    Review
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Chengshuo Fei *Division of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Yanlin Chen *Division of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Ruiqian Tan *Division of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Xinxing YangDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Guanda WuDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Chenglong LiDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Jiawei ShiDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Shiyong LeDivision of Spine Surgery, Department of Orthopaedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China.
Wenjie YangDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Jiajia XuDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. xujiajia@smu.edu.cn.
Liang WangDivision of Spine Surgery, Department of Orthopaedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China. wl3388@smu.edu.cn.
Zhongmin ZhangDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. zzmzzc@smu.edu.cn.

Funding

National Key Research and Development Program of China 2022YFC2502901National Key Research and Development Program of China 2022YFC2502904National Natural Science Foundation of China 2020A82272527
6 · The paper itself

Abstract

backgroundLigamentum flavum hypertrophy (LFH) is a primary contributor to lumbar spinal stenosis. However, a thorough understanding of the cellular and molecular mechanisms driving LFH fibrotic progression remains incomplete.

methodsSingle-cell RNA sequencing (scRNA-seq) was performed to construct the single-cell map of human ligamentum flavum (LF) samples. An integrated multi-omics approach, encompassing scRNA-seq, bulk RNA sequencing (bulk RNA-seq), and Mendelian randomization (MR), was applied to conduct comprehensive functional analysis. Clinical tissue specimens and animal models were employed to further confirm the multi-omics findings.

resultsScRNA-seq provided a single-cell level view of the fibrotic microenvironment in LF, revealing significantly increased proportions of fibroblasts, myofibroblasts, and macrophages in LFH. Using transmission electron microscopy, single-cell gene set scoring, and MR analysis, ferroptosis was identified as a critical risk factor and pathway within LFH. Subcluster analysis of fibroblasts revealed functional heterogeneity among distinct subpopulations, highlighting the functional characteristics and the metabolic dynamics of fibroblast with a high ferroptosis score (High Ferro-score FB). The quantification of gene expression at single-cell level revealed that ferroptosis increased along with fibrosis in LFH specimens, a finding further validated in both human and mice tissue sections. Consistently, bulk RNA-seq confirmed increased proportions of fibroblasts and macrophages in LFH specimens, underscoring a strong correlation between these cell types through Spearman correlation analysis. Notably, subcluster analysis of the mononuclear phagocytes identified a specific subset of SPP1

conclusionsOur findings indicated that SPP1

Indexed as

FerroptosisFibrosisLigamentum flavum hypertrophyMacrophages.Multi-omics analysisSingle-cell RNA sequencing

Identifiers

PMID40001138
PMCPMC11863437

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