RT Journal Article
SR Electronic
T1 Single-cell RNA-seq analysis reveals the progression of human osteoarthritis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 100
OP 110
DO 10.1136/annrheumdis-2017-212863
VO 78
IS 1
A1 Quanbo Ji
A1 Yuxuan Zheng
A1 Guoqiang Zhang
A1 Yuqiong Hu
A1 Xiaoying Fan
A1 Yu Hou
A1 Lu Wen
A1 Li Li
A1 Yameng Xu
A1 Yan Wang
A1 Fuchou Tang
YR 2019
UL http://ard.bmj.com/content/78/1/100.abstract
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.