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
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.
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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
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