Single-cell transcriptomics reveals variable trajectories of CSPCs in the progression of osteoarthritis
Osteoarthritis (OA) is characterised by cartilage destruction; however, there are no specific drugs available for its treatment. Cartilage-derived stem/progenitor cells (CSPCs) are multipotent cells that play an essential role in cartilage renewal and may provide critical insights into the medical n...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022024367 |
| _version_ | 1811213890906750976 |
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| author | Lingbin Qi Jian Wang Xian Chen Yanhui Ding Bin Ling Wenjun Wang Jun Xu Zhigang Xue |
| author_facet | Lingbin Qi Jian Wang Xian Chen Yanhui Ding Bin Ling Wenjun Wang Jun Xu Zhigang Xue |
| author_sort | Lingbin Qi |
| collection | DOAJ |
| description | Osteoarthritis (OA) is characterised by cartilage destruction; however, there are no specific drugs available for its treatment. Cartilage-derived stem/progenitor cells (CSPCs) are multipotent cells that play an essential role in cartilage renewal and may provide critical insights into the medical needs for OA treatment. However, alterations in cell function and fate of CSPCs during OA progression have seldom been analysed, especially at the single-cell level. Additionally, it has been reported that CSPCs can migrate to the cartilage injury area, although the mechanism of migration remains elusive. Thus, understanding the changing patterns of CSPCs in the pathological process of OA is important in the effort to develop stem cell therapy for OA. Here, we downloaded single-cell transcriptomic data of patients with OA from the Gene Expression Omnibus (GEO) database and performed unbiased clustering of the cells based on gene expression patterns using the Seurat package. Using common stem cell markers and chondrogenic transcription factors, we traced CSPCs throughout all stages of OA. We further explored the dynamics of CSPCs in OA progression and validated the single-cell RNA sequencing data in vitro using qPCR, immunofluorescence, and western blotting. Specifically, we primarily explored the heterogeneity of CSPCs at the single-cell level and found that it was closely associated with OA progression. Our results indicate significantly reduced chondrogenic differentiation capacity in CSPCs during the late stage of OA, while their proliferation capacity tended to increase. We also found that genes implicated in fibrosis, cell motility, and extracellular matrix remodelling were upregulated in CSPCs during the progression of OA. Our study revealed the dynamics of stem cells in OA progression and may inform the development of stem cell therapy for OA. |
| first_indexed | 2024-04-12T05:53:59Z |
| format | Article |
| id | doaj.art-4785f8c242f143cfb447a3b8977d908b |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-12T05:53:59Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-4785f8c242f143cfb447a3b8977d908b2022-12-22T03:45:13ZengElsevierHeliyon2405-84402022-11-01811e11148Single-cell transcriptomics reveals variable trajectories of CSPCs in the progression of osteoarthritisLingbin Qi0Jian Wang1Xian Chen2Yanhui Ding3Bin Ling4Wenjun Wang5Jun Xu6Zhigang Xue7Tongji Hospital, School of Medicine, Tongji University, Shanghai 200092, ChinaShanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, ChinaTongji Hospital, School of Medicine, Tongji University, Shanghai 200092, ChinaTongji Hospital, School of Medicine, Tongji University, Shanghai 200092, ChinaThe Second People’s Hospital of Yunnan Province, Kunming, ChinaStem Cell and Regenerative Medicine Engineering Research Center of Hunan Province, Hunan Yuanpin Cell Technology Co. Ltd, 102 Dongwu Road, Changsha City 410100, Hunan Province, China; Corresponding author.Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Corresponding author.Tongji Hospital, School of Medicine, Tongji University, Shanghai 200092, China; Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, Tongji University, 200065 Shanghai, China; Corresponding author.Osteoarthritis (OA) is characterised by cartilage destruction; however, there are no specific drugs available for its treatment. Cartilage-derived stem/progenitor cells (CSPCs) are multipotent cells that play an essential role in cartilage renewal and may provide critical insights into the medical needs for OA treatment. However, alterations in cell function and fate of CSPCs during OA progression have seldom been analysed, especially at the single-cell level. Additionally, it has been reported that CSPCs can migrate to the cartilage injury area, although the mechanism of migration remains elusive. Thus, understanding the changing patterns of CSPCs in the pathological process of OA is important in the effort to develop stem cell therapy for OA. Here, we downloaded single-cell transcriptomic data of patients with OA from the Gene Expression Omnibus (GEO) database and performed unbiased clustering of the cells based on gene expression patterns using the Seurat package. Using common stem cell markers and chondrogenic transcription factors, we traced CSPCs throughout all stages of OA. We further explored the dynamics of CSPCs in OA progression and validated the single-cell RNA sequencing data in vitro using qPCR, immunofluorescence, and western blotting. Specifically, we primarily explored the heterogeneity of CSPCs at the single-cell level and found that it was closely associated with OA progression. Our results indicate significantly reduced chondrogenic differentiation capacity in CSPCs during the late stage of OA, while their proliferation capacity tended to increase. We also found that genes implicated in fibrosis, cell motility, and extracellular matrix remodelling were upregulated in CSPCs during the progression of OA. Our study revealed the dynamics of stem cells in OA progression and may inform the development of stem cell therapy for OA.http://www.sciencedirect.com/science/article/pii/S2405844022024367Cartilage-derived stem cellsHeterogeneitySingle cellRNA-seqOsteoarthritis |
| spellingShingle | Lingbin Qi Jian Wang Xian Chen Yanhui Ding Bin Ling Wenjun Wang Jun Xu Zhigang Xue Single-cell transcriptomics reveals variable trajectories of CSPCs in the progression of osteoarthritis Heliyon Cartilage-derived stem cells Heterogeneity Single cell RNA-seq Osteoarthritis |
| title | Single-cell transcriptomics reveals variable trajectories of CSPCs in the progression of osteoarthritis |
| title_full | Single-cell transcriptomics reveals variable trajectories of CSPCs in the progression of osteoarthritis |
| title_fullStr | Single-cell transcriptomics reveals variable trajectories of CSPCs in the progression of osteoarthritis |
| title_full_unstemmed | Single-cell transcriptomics reveals variable trajectories of CSPCs in the progression of osteoarthritis |
| title_short | Single-cell transcriptomics reveals variable trajectories of CSPCs in the progression of osteoarthritis |
| title_sort | single cell transcriptomics reveals variable trajectories of cspcs in the progression of osteoarthritis |
| topic | Cartilage-derived stem cells Heterogeneity Single cell RNA-seq Osteoarthritis |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022024367 |
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