Cargando…

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

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 us...

Descripción completa

Detalles Bibliográficos
Autores principales: Ji, Quanbo, Zheng, Yuxuan, Zhang, Guoqiang, Hu, Yuqiong, Fan, Xiaoying, Hou, Yu, Wen, Lu, Li, Li, Xu, Yameng, Wang, Yan, Tang, Fuchou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317448/
https://www.ncbi.nlm.nih.gov/pubmed/30026257
http://dx.doi.org/10.1136/annrheumdis-2017-212863
_version_ 1783384747246878720
author Ji, Quanbo
Zheng, Yuxuan
Zhang, Guoqiang
Hu, Yuqiong
Fan, Xiaoying
Hou, Yu
Wen, Lu
Li, Li
Xu, Yameng
Wang, Yan
Tang, Fuchou
author_facet Ji, Quanbo
Zheng, Yuxuan
Zhang, Guoqiang
Hu, Yuqiong
Fan, Xiaoying
Hou, Yu
Wen, Lu
Li, Li
Xu, Yameng
Wang, Yan
Tang, Fuchou
author_sort Ji, Quanbo
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6317448
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BMJ Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-63174482019-01-14 Single-cell RNA-seq analysis reveals the progression of human osteoarthritis Ji, Quanbo Zheng, Yuxuan Zhang, Guoqiang Hu, Yuqiong Fan, Xiaoying Hou, Yu Wen, Lu Li, Li Xu, Yameng Wang, Yan Tang, Fuchou Ann Rheum Dis Osteoarthritis 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. BMJ Publishing Group 2019-01 2018-07-19 /pmc/articles/PMC6317448/ /pubmed/30026257 http://dx.doi.org/10.1136/annrheumdis-2017-212863 Text en © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Osteoarthritis
Ji, Quanbo
Zheng, Yuxuan
Zhang, Guoqiang
Hu, Yuqiong
Fan, Xiaoying
Hou, Yu
Wen, Lu
Li, Li
Xu, Yameng
Wang, Yan
Tang, Fuchou
Single-cell RNA-seq analysis reveals the progression of human osteoarthritis
title Single-cell RNA-seq analysis reveals the progression of human osteoarthritis
title_full Single-cell RNA-seq analysis reveals the progression of human osteoarthritis
title_fullStr Single-cell RNA-seq analysis reveals the progression of human osteoarthritis
title_full_unstemmed Single-cell RNA-seq analysis reveals the progression of human osteoarthritis
title_short Single-cell RNA-seq analysis reveals the progression of human osteoarthritis
title_sort single-cell rna-seq analysis reveals the progression of human osteoarthritis
topic Osteoarthritis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317448/
https://www.ncbi.nlm.nih.gov/pubmed/30026257
http://dx.doi.org/10.1136/annrheumdis-2017-212863
work_keys_str_mv AT jiquanbo singlecellrnaseqanalysisrevealstheprogressionofhumanosteoarthritis
AT zhengyuxuan singlecellrnaseqanalysisrevealstheprogressionofhumanosteoarthritis
AT zhangguoqiang singlecellrnaseqanalysisrevealstheprogressionofhumanosteoarthritis
AT huyuqiong singlecellrnaseqanalysisrevealstheprogressionofhumanosteoarthritis
AT fanxiaoying singlecellrnaseqanalysisrevealstheprogressionofhumanosteoarthritis
AT houyu singlecellrnaseqanalysisrevealstheprogressionofhumanosteoarthritis
AT wenlu singlecellrnaseqanalysisrevealstheprogressionofhumanosteoarthritis
AT lili singlecellrnaseqanalysisrevealstheprogressionofhumanosteoarthritis
AT xuyameng singlecellrnaseqanalysisrevealstheprogressionofhumanosteoarthritis
AT wangyan singlecellrnaseqanalysisrevealstheprogressionofhumanosteoarthritis
AT tangfuchou singlecellrnaseqanalysisrevealstheprogressionofhumanosteoarthritis