A single-cell atlas depicting the cellular and molecular features in human ligamental degeneration: a single cell combined spatial transcriptomics study

  1. Runze Yang
  2. Tianhao Xu
  3. Lei Zhang
  4. Minghao Ge
  5. Liwei Yan
  6. Jian Li
  7. Weili Fu  Is a corresponding author
  1. West China Hospital of Sichuan University, China

Abstract

Background: To systematically identify cell types in the human ligament, investigate how ligamental cell identities, functions, and interactions participated in the process of ligamental degeneration, and explore the changes of ligamental microenvironment homeostasis in the disease progression.

Methods: Using single-cell RNA sequencing and spatial RNA sequencing of approximately 49356 cells, we created a comprehensive cell atlas of healthy and degenerated human anterior cruciate ligaments. We explored the variations of the cell subtypes' spatial distributions and the different processes involved in the disease progression, linked them with the ligamental degeneration process using computational analysis, and verified findings with immunohistochemical and immunofluorescent staining.

Results: We identified new fibroblast subgroups that contributed to the disease, mapped out their spatial distribution in the tissue and revealed two dynamic trajectories in the process of the degenerative process. We compared the cellular interactions between different tissue states and identified important signaling pathways that may contribute to the disease.

Conclusion: This cell atlas provides the molecular foundation for investigating how ligamental cell identities, biochemical functions, and interactions contributed to the ligamental degeneration process. The discoveries revealed the pathogenesis of ligamental degeneration at the single-cell and spatial level, which is characterized by extracellular matrix remodeling. Our results provide new insights into the control of ligamental degeneration and potential clues to developing novel diagnostic and therapeutic strategies.

Funding: This study was funded by the National Natural Science Foundation of China (81972123, 82172508), Sichuan Science and Technology Program (2020YFH0075), Fundamental Research Funds for the Central Universities (2015SCU04A40), Chengdu Science and Technology Bureau Project (2019-YF05-00090-SN), and 1.3.5 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYJC21030, ZY2017301).

Data availability

Data are available in a public, open-access repository. The single-cell RNA-seq data and cluster annotations are available at GSA for human (https://ngdc.cncb.ac.cn/gsa-human/) with the accession number PRJCA014157.

Article and author information

Author details

  1. Runze Yang

    Department of Orthopedics, West China Hospital of Sichuan University, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Tianhao Xu

    Department of Orthopedics, West China Hospital of Sichuan University, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Lei Zhang

    Department of Orthopedics, West China Hospital of Sichuan University, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Minghao Ge

    Department of Orthopedics, West China Hospital of Sichuan University, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Liwei Yan

    Department of Orthopedics, West China Hospital of Sichuan University, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Jian Li

    Department of Orthopedics, West China Hospital of Sichuan University, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Weili Fu

    Department of Orthopedics, West China Hospital of Sichuan University, Chengdu, China
    For correspondence
    foxwin2008@163.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4438-2760

Funding

National Natural Science Foundation of China (81972123)

  • Weili Fu

National Natural Science Foundation of China (82172508)

  • Weili Fu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This study was reviewed and approved by our University Ethics Committee (Ethics Committee on Biomedical Research, West China Hospital of Sichuan University No. 658 2020-(921)) and all procedures complied with the Helsinki Declaration. Participants gave informed consent to participate in the study.

Copyright

© 2023, Yang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,031
    views
  • 190
    downloads
  • 5
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Runze Yang
  2. Tianhao Xu
  3. Lei Zhang
  4. Minghao Ge
  5. Liwei Yan
  6. Jian Li
  7. Weili Fu
(2023)
A single-cell atlas depicting the cellular and molecular features in human ligamental degeneration: a single cell combined spatial transcriptomics study
eLife 12:e85700.
https://doi.org/10.7554/eLife.85700

Share this article

https://doi.org/10.7554/eLife.85700

Further reading

    1. Cell Biology
    2. Medicine
    Wadih EI Khoury, Stephen Y Chan
    Insight

    In pulmonary hypertension, a combination of metabolic and mechanical dysfunction leads to irreversible vascular damage.

    1. Medicine
    Zhen Wang, Jie Zhu ... Xiang Zhou
    Research Article

    The incidence of post-cardiac arrest myocardial dysfunction (PAMD) is high, and there is currently no effective treatment available. This study aims to investigate the protective effects of exogenous mitochondrial transplantation in Sprague-Dawley (SD) rats. Exogenous mitochondrial transplantation can enhance myocardial function and improve the survival rate. Mechanistic studies suggest that mitochondrial transplantation can limit impairment in mitochondrial morphology, augment the activity of mitochondrial complexes II and IV, and raise ATP level. As well, mitochondrial therapy ameliorated oxidative stress imbalance, reduced myocardial injury, and thus improved PAMD after cardiopulmonary resuscitation (CPR).