Clinical Laboratory Department of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, 518172, China.
Shenzhen Key Laboratory of Metabolic Health, Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
Sci Rep. 2023 Sep 2;13(1):14467. doi: 10.1038/s41598-023-41874-z.
The patterns of communication among different chondrocyte subtypes in human cartilage degeneration and regeneration help us understand the microenvironment of osteoarthritis and optimize cell-targeted therapies. Here, a single-cell transcriptome dataset of chondrocytes is used to explore the synergistic and communicative patterns of different chondrocyte subtypes. We collected 1600 chondrocytes from 10 patients with osteoarthritis and analyzed the active communication patterns for the first time based on network analysis and pattern recognition at the single-cell level. Manifold learning and quantitative contrasts were performed to analyze conserved and specific communication pathways. We found that ProCs (Proliferative chondrocytes), ECs (Effector chondrocytes), preHTCs (Prehypertrophic chondrocytes), HTCs (Hypertrophic chondrocytes), and FCs (Fibrocartilage chondrocytes) are more active in incoming and outgoing signaling patterns, which is consistent with studies on their close functional cooperation. Among them, preHTCs play multiple roles in chondrocyte communication, and ProCs and preHTCs have many overlapping pathways. These two subtypes are the most active among all chondrocyte subtypes. Interestingly, ECs and FCs are a pair of "mutually exclusive" subtypes, of which ECs are predominant in incoming patterns and FCs in outgoing patterns. The active signaling pathways of ECs and FCs largely do not overlap. COLLAGEN and LAMININ are the main pivotal pathways, which means they are very important in the repair and expansion of joint homeostasis. Notably, only preHTCs assume multiple roles (including sender, receiver, mediator, and influencer) and are involved in multiple communication pathways. We have examined their communication patterns from the perspective of cellular interactions, revealed the relationships among different chondrocyte subtypes, and, in particular, identified a number of active subtypes and pathways that are important for targeted therapy in the osteoarthritic microenvironment. Our findings provide a new research paradigm and new insights into understanding chondrocyte activity patterns in the osteoarthritic microenvironment.
不同软骨细胞亚型在人类软骨退变和再生中的交流模式有助于我们了解骨关节炎的微环境，并优化针对细胞的治疗方法。在这里，我们使用软骨细胞的单细胞转录组数据集来探索不同软骨细胞亚型的协同和交流模式。我们从 10 名骨关节炎患者中收集了 1600 个软骨细胞，并首次基于网络分析和单细胞水平的模式识别分析了活跃的交流模式。我们进行了流形学习和定量对比，以分析保守和特定的通讯途径。我们发现 ProCs（增殖软骨细胞）、ECs（效应软骨细胞）、preHTCs（预肥大软骨细胞）、HTCs（肥大软骨细胞）和 FCs（纤维软骨细胞）在传入和传出信号模式中更活跃，这与它们密切的功能合作研究一致。其中，preHTCs 在软骨细胞通讯中发挥多种作用，ProCs 和 preHTCs 有许多重叠的途径。这两个亚型是所有软骨细胞亚型中最活跃的。有趣的是，ECs 和 FCs 是一对“互斥”的亚型，其中 ECs 在传入模式中占主导地位，而 FCs 在传出模式中占主导地位。ECs 和 FCs 的活跃信号通路在很大程度上没有重叠。COLLAGEN 和 LAMININ 是主要的关键途径，这意味着它们在关节内稳态的修复和扩张中非常重要。值得注意的是，只有 preHTCs 具有多种作用（包括发送方、接收方、调解方和影响方），并参与多种通讯途径。我们从细胞相互作用的角度检查了它们的通讯模式，揭示了不同软骨细胞亚型之间的关系，特别是确定了一些在骨关节炎微环境中针对特定治疗方法具有重要作用的活跃亚型和途径。我们的研究结果为理解骨关节炎微环境中软骨细胞的活性模式提供了新的研究范例和新的见解。
