■我们旨在研究滑膜成纤维细胞的异质性及其以单细胞的分辨率进行细胞状态转变的潜力。
■我们采用单细胞RNA测序(scRNA-seq)方法来全面绘制患有慢性肩袖撕裂(RCT)和急性肱骨近端骨折(PHFs)的个体肩关节滑膜的细胞图。利用无偏聚类分析,我们成功地鉴定了滑膜环境中不同的成纤维细胞亚群.我们利用Monocle3描绘了滑膜成纤维细胞状态转变的轨迹。我们使用CellPhoneDBv2.1.0来预测滑膜微环境中的细胞间通讯模式。
■我们确定了肩部滑膜中的八个主要细胞簇。无偏聚类分析确定了四个滑膜成纤维细胞亚群,具有与蛋白质分泌相关的多种生物学功能,ECM重塑,炎症调节和细胞分裂。衬里,间充质,确定促炎和增殖性成纤维细胞亚群。结合StemID和特征性基因特征的结果,间充质成纤维细胞表现出成纤维细胞祖细胞的特征。滑膜成纤维细胞状态转变的轨迹显示从间充质到促炎和衬里表型的转变。此外,与急性创伤相比,在退行性肩关节疾病中,成纤维细胞亚簇之间的串扰增加。
■我们成功地生成了肩关节滑膜的scRNA-seq转录组图谱,这提供了对滑膜成纤维细胞异质性的全面理解,他们经历状态转换的潜力,以及它们在慢性退行性和急性创伤性肩关节疾病中的细胞间通讯。
We aimed to investigate the heterogeneity of synovial fibroblasts and their potential to undergo cell state transitions at the resolution of single cells.
We employed the single-cell RNA sequencing (scRNA-seq) approach to comprehensively map the cellular landscape of the shoulder synovium in individuals with chronic rotator cuff tears (RCTs) and acute proximal humerus fractures (PHFs). Utilizing unbiased clustering analysis, we successfully identified distinct subpopulations of fibroblasts within the synovial environment. We utilized Monocle 3 to delineate the trajectory of synovial fibroblast state transition. And we used CellPhone DB v2.1.0 to predict cell-cell communication patterns within the synovial microenvironment.
We identified eight main cell clusters in the shoulder synovium. Unbiased clustering analysis identified four synovial fibroblast subpopulations, with diverse biological functions associated with protein secretion, ECM remodeling, inflammation regulation and cell division. Lining, mesenchymal, pro-inflammatory and proliferative fibroblasts subsets were identified. Combining the results from StemID and characteristic gene features, mesenchymal fibroblasts exhibited characteristics of fibroblast progenitor cells. The trajectory of synovial fibroblast state transition showed a transition from mesenchymal to pro-inflammatory and lining phenotypes. In addition, the cross talk between fibroblast subclusters increased in degenerative shoulder diseases compared to acute trauma.
We successfully generated the scRNA-seq transcriptomic atlas of the shoulder synovium, which provides a comprehensive understanding of the heterogeneity of synovial fibroblasts, their potential to undergo state transitions, and their intercellular communication in the context of chronic degenerative and acute traumatic shoulder diseases.