Abstract
AbstractBackgroundTo 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.MethodsUsing 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.ResultsWe 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.ConclusionThis 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.FundingThis 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).
Publisher
Cold Spring Harbor Laboratory