A single-cell atlas depicting the cellular and molecular features in human ligamental degeneration: a single cell combined spatial transcriptomics study
Abstract
Background
To systematically identify cell types in human ligament, investigate how ligamental cell identities, functions, and interactions participated 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 ligamental degeneration process using computational analysis.
Results
We identified new fibroblast subgroups contributed to the disease and mapped out their spatial distribution in the tissue and revealed two stages of the degenerative process. We compared the cellular interactions between different tissue states and identified important signaling pathways 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 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).
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