Single-cell and spatial transcriptomics reveal changes in cell heterogeneity during progression of human tendinopathy.
Single-cell and spatial transcriptomics reveal changes in cell heterogeneity during progression of human tendinopathy.
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DOI：
10.1186/s12915-023-01613-2
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发表时间：
2023-06-06
期刊：
影响因子：
5.4
通讯作者：
Li, Jian
中科院分区：
文献类型：
--
作者：
Fu, Weili;Yang, Runze;Li, Jian
肌肉骨骼组织退行性变损害了许多人的生活质量和运动功能，尤其是老年人和运动员。肌腱病是与肌肉骨骼组织退化相关的最常见疾病之一，是影响运动员和普通民众的主要全球医疗负担，临床表现为长期反复发作的慢性疼痛和活动耐受性下降。作为疾病过程基础的细胞和分子机制仍然难以捉摸。在这里，我们使用单细胞和空间RNA测序的方法来进一步了解细胞的异质性和肌腱病变进展的分子机制。为了探讨肌腱病变过程中肌腱动态平衡的变化，我们利用大约35,000个细胞的单细胞RNA测序建立了健康和疾病人肌腱的细胞图谱，并利用空间RNA测序探索了细胞亚型的空间分布的变化。我们对正常和损伤肌腱中不同的肌腱细胞亚群进行了鉴定和定位，发现正常和病变肌腱中肌腱干/祖细胞的分化轨迹不同，揭示了基质细胞和病变肌腱细胞之间的空间位置关系。我们在单细胞水平上破译了肌腱病的进展，其特征是炎症渗透，随后是软骨生成，最后是软骨内骨化。我们发现病变的组织特异性内皮细胞亚群和巨噬细胞是潜在的治疗靶点。该细胞图谱为研究肌腱细胞特性、生化功能和相互作用在肌腱病变过程中的作用提供了分子基础。这些发现揭示了肌腱病在单细胞和空间水平上的发病机制，其特征是炎症渗透，然后是软骨生成，最后是软骨内骨化。我们的结果为肌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的线索。网上版载有补充材料，可在10.1186/s12915-023-01613-2查阅。
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. The online version contains supplementary material available at 10.1186/s12915-023-01613-2.
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作者：
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