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DDX18 coordinates nucleolus phase separation and nuclear organization to control the pluripotency of human embryonic stem cells

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE182855 | GEO | 2024/11/13

REPOSITORIES: GEO

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DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells [RNA-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.

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DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells [DDX18_iCLIP-seq]

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SILAC of hESCs with DDX18 knockdown

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.

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DDX18 coordinates nucleolus phase separation and nuclear organization to control the pluripotency of human embryonic stem cells

Project description:DDX18 coordinates nucleolus phase separation and nuclear organization to control the pluripotency of human embryonic stem cells

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DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells.

Project description:DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells.

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DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells [DDX18_CHIP-seq]

Project description:DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells [DDX18_CHIP-seq]

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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 [DDX18_iCLIP-seq]

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DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells [RNA-seq]

Project description:DDX18 coordinates nucleolus phase separation and chromatin organization to control the pluripotency of human embryonic stem cells [RNA-seq]

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DDX18 safeguards rDNA epigenetic landscape by counteracting PRC2 and maintains ESC identity

Project description:Here we have RNA binding protein DDX18 connecting rRNA transcription to early embryo development and embryonic stem cell (ESC) identity maintenance. DDX18 mutant embryos suffer lethality during preimplantation development. DDX18 depletion impairs ESC self-renewal and pluripotency, which phenotype-copies RNA polymerase I (RNAPI) inhibition. Mechanistically, DDX18 is recruited to rDNA by RNAPI transcription machinery and senses rRNA transcription by binding to pre-rRNA. In nucleolus, DDX18 surrounds DFC ring and interacts with PRC2. In the presence of transcribed pre-rRNA, DDX18 interaction with PRC2 makes EZH2 unstably binding to the other components of PRC2, thereby preventing PRC2 engagement and counteracting H3K27me3 mediated silencing at rDNA chromatin. Together, our study shows that DDX18 plays important roles in safeguarding ESCs identity through regulating epigenetic states of rDNA locus and maintaining euchromatin structure in nucleolus.

2019-12-25 | GSE124580 | GEO

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