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| Status |
Public on Oct 11, 2018 |
| Title |
Stabilizing Heterochromatin by DGCR8 Alleviates Senescence and Osteoarthritis (RNA-seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
DiGeorge syndrome critical region 8 (DGCR8) is a critical component of the canonical microprocessor complex for microRNA biogenesis. However, the non-canonical functions of DGCR8 have not been studied. Here, we demonstrate that DGCR8 plays an important role in maintaining heterochromatin organization and preventing aging. An N-terminal-truncated version of DGCR8 (DR8dex2) accelerated senescence in human mesenchymal stem cells (hMSCs) independent of its miRNA-processing activity, which is mediated by its C-terminal domain. Further studies revealed that DGCR8 maintained heterochromatin organization by interacting with the nuclear envelope protein Lamin B1, and heterochromatin-associated proteins, KAP1 and HP1g expressing of any of these proteins, including DGCR8, reversed premature senescent phenotypes in DR8dex2 hMSCs. Finally, DGCR8 was downregulated in pathological and naturally aged hMSCs, whereas DGCR8 expressing alleviated hMSC aging and osteoarthritis in mice. Taken together, these analyses uncovered a novel, miRNA-independent role for DGCR8 in maintaining heterochromatin organization and preventing senescence. DGCR8 may therefore represent a new therapeutic target for alleviating human aging-related disorders.
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| Overall design |
Transcriptome analysis of knee joints tissues upon the treatment of lentiviruses expressing Luc, DR8-WT, or DR8-mtDRBD in anterior cruciate ligament transection (ACLT) induced osteoarthritis (OA) mouse model.
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| Contributor(s) |
Liu G |
| Citation(s) |
31350386 |
| |
| Submission date |
Oct 09, 2018 |
| Last update date |
Aug 06, 2019 |
| Contact name |
Zunpeng Liu |
| E-mail(s) |
zunpengliu@163.com
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| Phone |
+86 15510715055
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| Organization name |
State Key Laboratory of Stem Cell and Reproductive Biology
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| 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 (12)
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| Relations |
| BioProject |
PRJNA495379 |
| SRA |
SRP164765 |
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