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Maintenance of nucleolar homeostasis by CBX4 alleviates senescence and osteoarthritis

ABSTRACT: Maintenance of nucleolar homeostasis by CBX4 alleviates senescence and osteoarthritis

PROVIDER: PRJNA515848 | ENA |

REPOSITORIES: ENA

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Maintenance of nucleolar homeostasis by CBX4 alleviates senescence and osteoarthritis

Project description: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.

2019-01-19 | GSE125320 | GEO

Safeguarding nucleolar homeostasis by CBX4 alleviates senescence and osteoarthritis

Project description:Chromobox homolog 4 (CBX4), a component of polycomb repressive complexes 1 (PRC1), plays important roles in the maintenance of cell identity and organism development through epigenetic silencing. However, it remains unclear whether CBX4 regulates the homeostasis of human stem cells. Here, we demonstrate that CBX4 counteracts human mesenchymal stem cell (hMSC) aging via the maintenance of nucleolar homeostasis. CBX4 protein decreases in aged hMSCs, and targeted knockout of CBX4 in young hMSCs destabilizes nucleolar heterochromatin, increases ribosome biogenesis, and accelerates cellular senescence. CBX4 maintains nucleolar homeostasis by recruiting fibrillarin at nucleolar rDNA repeats, limiting excessive expression of rRNAs. Importantly, overexpression of CBX4 expression alleviates physiological hMSC aging as well as attenuates the development of post-traumatic osteoarthritis in mice. Taken together, our study uncovers a novel role of CBX4 in counteracting senescence by maintaining nucleolar homeostasis, providing a potential therapeutic target for aging-associated disorders.

2019-07-13 | GSE117084 | GEO

Safeguarding nucleolar homeostasis by CBX4 alleviates senescence and osteoarthritis

Project description:Safeguarding nucleolar homeostasis by CBX4 alleviates senescence and osteoarthritis

| PRJNA481020 | ENA

Maintenance of nucleolar homeostasis by PC2 alleviates senescence and osteoarthritis

Project description:Polycomb 2 protein (PC2), 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 PC2 regulates the homeostasis of human stem cells remains unclear. Here, we demonstrate that PC2 counteracts human mesenchymal stem cell (hMSC) aging via the maintenance of nucleolar homeostasis. PC2 protein is decreased in aged hMSCs, and targeted PC2 knockout in young hMSCs results in destabilized nucleolar heterochromatin, increased ribosome biogenesis and protein translation, and accelerated cellular senescence. PC2 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 PC2 alleviates physiological hMSC aging and attenuates the development of posttraumatic osteoarthritis in mice. Taken together, our findings reveal a novel role of PC2 in counteracting senescence by maintaining nucleolar homeostasis, providing a potential therapeutic target for aging-associated disorders.

2018-10-10 | GSE121033 | GEO

Maintenance of nucleolar homeostasis by PC2 alleviates senescence and osteoarthritis

Project description:Maintenance of nucleolar homeostasis by PC2 alleviates senescence and osteoarthritis

| PRJNA495384 | ENA

Stabilizing Heterochromatin by DGCR8 Alleviates Senescence and Osteoarthritis

Project description:Stabilizing Heterochromatin by DGCR8 Alleviates Senescence and Osteoarthritis

| PRJNA450075 | ENA

Upregulation of FOXD1 by YAP alleviates senescence and osteoarthritis

Project description:Upregulation of FOXD1 by YAP alleviates senescence and osteoarthritis

| PRJNA433339 | ENA

Stabilizing Heterochromatin by DGCR8 Alleviates Senescence and Osteoarthritis (RNA-seq)

Project description:Stabilizing Heterochromatin by DGCR8 Alleviates Senescence and Osteoarthritis (RNA-seq)

| PRJNA495379 | ENA

Stabilizing Heterochromatin by DGCR8 Alleviates Senescence and Osteoarthritis (ChIP-Seq)

Project description:Stabilizing Heterochromatin by DGCR8 Alleviates Senescence and Osteoarthritis (ChIP-Seq)

| PRJNA450388 | ENA

Exosomes from antler stem cells alleviates MSC senescence and osteoarthritis

Project description:Exosomes from antler stem cells alleviates MSC senescence and osteoarthritis

| PRJNA723295 | ENA

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