PT  - JOURNAL ARTICLE
AU  - Quanbo Ji
AU  - Yuxuan Zheng
AU  - Guoqiang Zhang
AU  - Yuqiong Hu
AU  - Xiaoying Fan
AU  - Yu Hou
AU  - Lu Wen
AU  - Li Li
AU  - Yameng Xu
AU  - Yan Wang
AU  - Fuchou Tang
TI  - Single-cell RNA-seq analysis reveals the progression of human osteoarthritis
AID  - 10.1136/annrheumdis-2017-212863
DP  - 2019 Jan 01
TA  - Annals of the Rheumatic Diseases
PG  - 100--110
VI  - 78
IP  - 1
4099  - http://ard.bmj.com/content/78/1/100.short
4100  - http://ard.bmj.com/content/78/1/100.full
SO  - Ann Rheum Dis2019 Jan 01; 78
AB  - Objectives 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).Methods 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 and correspondence analysis.Results We identified seven molecularly defined populations of chondrocytes in the human OA cartilage, including three novel phenotypes with distinct functions. We presented gene expression profiles 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.Conclusions Our results provide new insights into chondrocyte taxonomy and present potential clues for effective and functional manipulation of human OA cartilage regeneration that could lead to improved health.