Single-cell RNA-seq analysis reveals the progression of human osteoarthritis

Understanding the molecular mechanisms underlying human cartilage degeneration and regeneration is helpful for improving therapeutic strategies for treating osteoarthritis (OA). Here, we report the molecular programmes and lineage progression patterns controlling human OA pathogenesis using single-cell RNA sequencing (scRNA-seq). We performed unbiased transcriptome-wide scRNA-seq analysis, computational analysis and histological assays on 1464 chondrocytes from 10 patients with OA undergoing knee arthroplasty surgery. We investigated the relationship between transcriptional programmes of the OA landscape and clinical outcome using severity index analysis and correspondence analysis. We identified seven molecularly defined populations of chondrocytes in human OA cartilage, including three novel phenotypes with distinct functions. We presented gene expression profiles and transcriptional networks among chondrocytes at different OA stages at single-cell resolution. We found a potential transition among proliferative chondrocytes, prehypertrophic chondrocytes and hypertrophic chondrocytes (HTCs) and defined a new subdivision within HTCs. We revealed novel markers for cartilage progenitor cells (CPCs) and demonstrated a relationship between CPCs and fibrocartilage chondrocytes using computational analysis. Notably, we derived predictive targets with respect to clinical outcomes and clarified the role of different cell types for the early diagnosis and treatment of OA. 34 Samples

解析人类软骨退变与再生的分子机制，有助于优化骨关节炎（osteoarthritis, OA）的治疗策略。本研究借助单细胞RNA测序（single-cell RNA sequencing, scRNA-seq），揭示了调控人类骨关节炎发病进程的分子调控程序与谱系发育模式。我们对10名接受膝关节置换手术的骨关节炎患者的1464个软骨细胞开展了无偏倚的全转录组测序分析、计算分析与组织学检测。通过严重程度指数分析及对应分析，我们探究了骨关节炎转录组特征与临床结局之间的关联。我们在人类骨关节炎软骨中鉴定出7个经分子定义的软骨细胞群，其中包含3个具备独特功能的全新表型。我们以单细胞分辨率呈现了不同骨关节炎分期下软骨细胞的基因表达谱与转录调控网络。我们发现增殖性软骨细胞、前肥大软骨细胞与肥大软骨细胞（hypertrophic chondrocytes, HTCs）之间存在潜在的转化关系，并明确了肥大软骨细胞内部的新亚型细分。我们揭示了软骨祖细胞（cartilage progenitor cells, CPCs）的新型标志物，并通过计算分析阐明了软骨祖细胞与纤维软骨软骨细胞之间的关联。值得注意的是，我们推导得到与临床结局相关的预测靶点，并明确了不同细胞类型在骨关节炎早期诊断与治疗中的作用。34例样本

搜集汇总

背景与挑战

背景概述

该数据集是一个单细胞RNA测序研究，聚焦人类骨关节炎进展。它包含来自10名患者的1464个软骨细胞的高通量测序数据，识别了7种分子定义的软骨细胞群，并揭示了新标记物和细胞类型转换，旨在为早期诊断和治疗提供预测目标。