DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells [DDX18_CHIP-seq]
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ABSTRACT: DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells [DDX18_CHIP-seq]
Project description:Pluripotent stem cells are unique in their large nucleus and manifestly open chromatin structure with hypertranscriptional activities. How the nucleolus, the largest membraneless and phase-separated subnuclear organelle, maintains its structural integrity in pluripotency maintenance remains incompletely understood. By studying nucleolus-specific DEAD-box RNA helicase-18 (DDX18) in human embryonic stem cells, we discover mechanisms controlling nucleolus phase separation and chromatin organization.
Project description:Pluripotent stem cells are unique in their large nucleus and manifestly open chromatin structure with hypertranscriptional activities. How the nucleolus, the largest membraneless and phase-separated subnuclear organelle, maintains its structural integrity in pluripotency maintenance remains incompletely understood. By studying nucleolus-specific DEAD-box RNA helicase-18 (DDX18) in human embryonic stem cells, we discover mechanisms controlling nucleolus phase separation and chromatin organization.
Project description:Pluripotent stem cells are unique in their large nucleus and manifestly open chromatin structure with hypertranscriptional activities. How the nucleolus, the largest membraneless and phase-separated subnuclear organelle, maintains its structural integrity in pluripotency maintenance remains incompletely understood. By studying nucleolus-specific DEAD-box RNA helicase-18 (DDX18) in human embryonic stem cells, we discover mechanisms controlling nucleolus phase separation and chromatin organization.
Project description:Pluripotent stem cells are unique in their large nucleus and manifestly open chromatin structure with hypertranscriptional activities. How the nucleolus, the largest membraneless and phase-separated subnuclear organelle, maintains its structural integrity in pluripotency maintenance remains incompletely understood. By studying nucleolus-specific DEAD-box RNA helicase-18 (DDX18) in human embryonic stem cells, we discover mechanisms controlling nucleolus phase separation and chromatin organization.
Project description:This study explores the crucial role of the nucleolus-specific RNA helicase DDX18 in maintaining the pluripotency of human embryonic stem cells. We demonstrate that DDX18 coordinates nucleolus phase separation and chromatin organization by interacting with NPM1 in the granular component of the nucleolus, facilitated by nucleolar RNA species. The absence of DDX18 disrupts immiscible nucleolar substructures, significantly affecting centromere clustering and perinucleolar heterochromatin (PNH) formation.
Project description:DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells [DDX18_iCLIP-seq]
Project description:DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells [RNA-seq]
Project description:Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs. Loss of DDX18 disrupts nucleolar substructures, impairing centromere clustering and perinucleolar heterochromatin (PNH) formation. To probe this further, we develop NoCasDrop, a tool enabling precise nucleolar targeting and controlled liquid condensation, which restores centromere clustering and PNH integrity while modulating developmental gene expression. This study reveals how nucleolar phase separation dynamics govern chromatin organization and cell fate, offering fresh insights into the molecular regulation of stem cell pluripotency.