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| Status |
Public on Jan 19, 2019 |
| Title |
Maintenance of nucleolar homeostasis by CBX4 alleviates senescence and osteoarthritis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
CBX4, a component of polycomb repressive complex 1 (PRC1), plays important roles in the maintenance of cell identity and organ development through epigenetic silencing. However, whether CBX4 regulates the homeostasis of human stem cells remains unclear. Here, we demonstrate that CBX4 counteracts human mesenchymal stem cell (hMSC) aging via the maintenance of nucleolar homeostasis. CBX4 protein is decreased in aged hMSCs, and targeted CBX4 knockout in young hMSCs results in destabilized nucleolar heterochromatin, increased ribosome biogenesis and protein translation, and accelerated cellular senescence. CBX4 maintains nucleolar homeostasis by recruiting nucleolar protein fibrillarin and heterochromatin organization associated protein KAP1 at nucleolar rDNA, limiting the excessive expression of rRNAs. Importantly, overexpression of CBX4 alleviates physiological hMSC aging and attenuates the development of posttraumatic osteoarthritis in mice. Taken together, our findings reveal a novel role of CBX4 in counteracting senescence by maintaining nucleolar homeostasis, providing a potential therapeutic target for aging-associated disorders.
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| Overall design |
Transcriptome analysis of knee joints tissues upon the treatment of lentiviruses expressing Luc, CBX4 in anterior cruciate ligament transection (ACLT) induced osteoarthritis (OA) mouse model.
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| Contributor(s) |
Liu G |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Jan 18, 2019 |
| Last update date |
Mar 01, 2019 |
| Contact name |
Zunpeng Liu |
| E-mail(s) |
zunpengliu@163.com
|
| Phone |
+86 15510715055
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| Organization name |
State Key Laboratory of Stem Cell and Reproductive Biology
|
| Department |
Institute of Zoology, Chinese Academy of Sciences
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| Lab |
Jing Qu
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| Street address |
Beichen West Road
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| City |
Beijing |
| ZIP/Postal code |
100101 |
| Country |
China |
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| Platforms (1) |
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| Samples (9)
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| GSM3568918 |
OA model_Lentiviruses expressing Luc rep1 |
| GSM3568919 |
OA model_Lentiviruses expressing Luc rep2 |
| GSM3568920 |
OA model_Lentiviruses expressing Luc rep3 |
| GSM3568921 |
OA model_Lentiviruses expressing CBX4 rep1 |
| GSM3568922 |
OA model_Lentiviruses expressing CBX4 rep2 |
| GSM3568923 |
OA model_Lentiviruses expressing CBX4 rep3 |
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| Relations |
| BioProject |
PRJNA515848 |
| SRA |
SRP180201 |
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