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Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome
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Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling
Feifei Liu1, Yi Lu2, Xuebao Wang3,4
1State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Protein & Cell
|December 13, 2023
Summary
Aging synovium contributes to joint pain. This study reveals forkhead box O1 (FOXO1) downregulation in aged synovial mesenchymal stromal cells (MSCs), highlighting its role in joint aging and potential therapeutic targets.
Area of Science:
- Gerontology
- Orthopedics
- Molecular Biology
Background:
- The synovium, crucial for joint lubrication, changes with age, contributing to joint diseases and pain.
- Mechanisms of human synovial aging are not well understood, hindering effective joint degeneration treatments.
Purpose of the Study:
- To comprehensively profile transcriptomic changes in human synovial cells during aging.
- To identify key molecular regulators and cellular pathways involved in synovial aging.
Main Methods:
- Generated transcriptomic profiles of synovial cells from young and aged individuals.
- Analyzed differential gene expression and cell-cell communication networks.
- Investigated the role of forkhead box O1 (FOXO1) in synovial mesenchymal stromal cells (MSCs).
Main Results:
- Identified two MSC subsets (lining and sublining) in human synovium.
- Observed upregulated angiogenesis and fibrosis genes, and downregulated cell adhesion and cartilage genes in aged MSCs.
- Found FOXO1 downregulation in aged synovial MSCs, which was recapitulated in FOXO1-depleted MSCs, inducing senescence.
Conclusions:
- FOXO1 plays a critical role in regulating human synovial aging.
- Understanding synovial aging mechanisms, particularly FOXO1's role, can inform strategies for joint rejuvenation.
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