Single-cell analysis of the somatic mutational landscape in human chondrocytes during aging and in osteoarthritis
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Abstract
Abstract Somatic mutation is now recognized as a cause of multiple human diseases other than cancer. Osteoarthritis (OA), a highly prevalent age-related disease, has been associated with increased chromosomal abnormalities in articular cartilage of OA patients. Thus far no systematic attempt has been made to characterize the somatic mutational landscape of chondrocytes during normal aging and in affected cartilage of OA patients. Here we used single-cell whole genome sequencing to quantitatively analyze single-nucleotide variants (SNVs) and small insertions and deletions (InDels) in 100 single chondrocytes isolated from the cartilage of hip femoral heads of 17 subjects aged from 26 to 90 years, including 9 OA patients and 8 non-OA donors. Both SNVs and InDels were found to accumulate with age in chondrocytes with a clock-like mutational signature. Surprisingly, the age-related accumulation rate of these mutations was found to be lower in OA chondrocytes compared with chondrocytes from non-OA control subjects.
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Ying, K., Bie, J., Chen, G., Cuervo, A. M., Deng, H., Dong, L., Furman, D., Gorbunova, V., Han, J. J., Horvath, S., et al. (2026) · Nature Aging · doi:10.1038/s43587-026-01226-8
Self-citationZhang, J., Su, W., Duan, J., Sun, Y., & Liu, B. (2026) · The Innovation Life · doi:10.59717/j.xinn-life.2026.100262
- Authors
- Ren, P., Zheng, C., Pang, Y., Qiang, Y., Sun, S., Wang, Q., Xu, W., Lee, M., Lu, Z., Zhou, M., He, J., Liu, N., Maslov, A. Y., Dong, X., Zhang, C., Gao, J., & Vijg, J.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Albert Einstein College of Medicine (US)
- University of Minnesota (US)
- Corresponding author
- Dong, Xiao
- Zhang, Changqing
- Gao, Junjie
- Vijg, Jan
- ORCID
- Venue
- Nature Aging
- Published
- 2025-11-17
- Volume
- 5
- Issue
- 12
- Pages
- 2417-2431
- ISSN
- 2662-8465 (ISSN-L)
- PMC
- PMC12705439
- OpenAlex
- W4416299107
- Cited by
- 6
- References
- 84
- Citations by year
- 2026: 5 · 2025: 1
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Aging (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- Funders
- National Natural Science Foundation of China (82172461)
- National Key Research and Development Program of China
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- somatic mutations, chondrocytes, osteoarthritis, aging, articular cartilage, single nucleotide variants, indels, mutational signatures, DNA damage, chondrocyte death, structural variants
- MeSH terms
- Whole Genome Sequencing, Adult, Aged, Aged, 80 and over, Aging, Cartilage, Articular, Female, Humans, Male, Middle Aged, Mutation, Osteoarthritis, Chondrocytes, Polymorphism, Single Nucleotide, INDEL Mutation, Single-Cell Analysis
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