Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
BMC Biol. 2023 Jun 6;21(1):132. doi: 10.1186/s12915-023-01613-2.
Musculoskeletal tissue degeneration impairs the life quality and motor function of many people, especially seniors and athletes. Tendinopathy is one of the most common diseases associated with musculoskeletal tissue degeneration, representing a major global healthcare burden that affects both athletes and the general population, with the clinical presentation of long-term recurring chronic pain and decreased tolerance to activity. The cellular and molecular mechanisms at the basis of the disease process remain elusive. Here, we use a single-cell and spatial RNA sequencing approach to provide a further understanding of cellular heterogeneity and molecular mechanisms underlying tendinopathy progression.
To explore the changes in tendon homeostasis during the tendinopathy process, we built a cell atlas of healthy and diseased human tendons using single-cell RNA sequencing of approximately 35,000 cells and explored the variations of cell subtypes' spatial distributions using spatial RNA sequencing. We identified and localized different tenocyte subpopulations in normal and lesioned tendons, found different differentiation trajectories of tendon stem/progenitor cells in normal/diseased tendons, and revealed the spatial location relationship between stromal cells and diseased tenocytes. We deciphered the progression of tendinopathy at a single-cell level, which is characterized by inflammatory infiltration, followed by chondrogenesis and finally endochondral ossification. We found diseased tissue-specific endothelial cell subsets and macrophages as potential therapeutic targets.
This cell atlas provides the molecular foundation for investigating how tendon cell identities, biochemical functions, and interactions contributed to the tendinopathy process. The discoveries revealed the pathogenesis of tendinopathy at single-cell and spatial levels, which is characterized by inflammatory infiltration, followed by chondrogenesis, and finally endochondral ossification. Our results provide new insights into the control of tendinopathy and potential clues to developing novel diagnostic and therapeutic strategies.
肌肉骨骼组织退化降低了许多人的生活质量和运动功能，尤其是老年人和运动员。腱病是与肌肉骨骼组织退化相关的最常见疾病之一，是一种主要的全球医疗保健负担，影响运动员和普通人群，其临床表现为长期反复发作的慢性疼痛和活动耐量降低。疾病进程的细胞和分子机制仍不清楚。在这里，我们使用单细胞和空间 RNA 测序方法，进一步了解腱病进展的细胞异质性和分子机制。
为了探索腱病过程中腱稳态的变化，我们使用单细胞 RNA 测序对大约 35000 个细胞进行了健康和患病人类肌腱的细胞图谱构建，并使用空间 RNA 测序探索了细胞亚型空间分布的变化。我们在正常和病变肌腱中鉴定并定位了不同的腱细胞亚群，发现了正常/病变肌腱中肌腱干/祖细胞的不同分化轨迹，并揭示了基质细胞与病变腱细胞之间的空间位置关系。我们在单细胞水平上破译了腱病的进展，其特征是炎症浸润，随后是软骨生成，最后是软骨内骨化。我们发现了病变组织特异性内皮细胞亚群和巨噬细胞作为潜在的治疗靶点。
该细胞图谱为研究肌腱细胞特性、生化功能和相互作用如何导致腱病进程提供了分子基础。这些发现揭示了腱病在单细胞和空间水平上的发病机制，其特征是炎症浸润，随后是软骨生成，最后是软骨内骨化。我们的研究结果为腱病的控制提供了新的见解，并为开发新的诊断和治疗策略提供了潜在线索。
