# DDX18 Regulates Nucleolus Phase Separation and Nuclear Organization to Maintain Pluripotency in Human Embryonic Stem Cells
Human embryonic stem cells (hESCs) are a cornerstone of regenerative medicine and developmental biology due to their unique ability to self-renew indefinitely and differentiate into all cell types of the human body. These remarkable properties, collectively referred to as pluripotency, are tightly regulated by a complex interplay of molecular mechanisms. Recent research has shed light on the role of DDX18, a DEAD-box RNA helicase, in maintaining pluripotency by regulating nucleolus phase separation and nuclear organization. This article explores the emerging evidence and mechanisms underlying DDX18’s critical role in hESC biology.
—
## The Nucleolus: A Hub for Cellular Organization and Function
The nucleolus is a dynamic, membrane-less organelle within the nucleus that plays a central role in ribosome biogenesis, stress response, and cellular homeostasis. It is formed through liquid-liquid phase separation (LLPS), a process by which biomolecules condense into distinct compartments without the need for a surrounding membrane. The nucleolus is also increasingly recognized as a key regulator of nuclear organization and gene expression.
In hESCs, the nucleolus is not only essential for ribosome production but also serves as a platform for maintaining the unique chromatin architecture and transcriptional programs required for pluripotency. Disruption of nucleolar function can lead to loss of pluripotency and differentiation, underscoring its importance in stem cell biology.
—
## DDX18: A Multifunctional RNA Helicase
DDX18 belongs to the DEAD-box family of RNA helicases, which are involved in various aspects of RNA metabolism, including transcription, splicing, ribosome assembly, and RNA transport. DDX18 has been implicated in ribosomal RNA (rRNA) processing and nucleolar organization, but its role in hESCs has only recently come to light.
Emerging studies suggest that DDX18 is a critical regulator of nucleolar phase separation and nuclear organization in hESCs. By modulating these processes, DDX18 helps maintain the transcriptional and epigenetic landscape required for pluripotency.
—
## DDX18 and Nucleolus Phase Separation
Phase separation in the nucleolus is driven by interactions between proteins and RNA, which form dynamic condensates. DDX18 has been shown to interact with rRNA and nucleolar proteins, facilitating the proper assembly and maintenance of nucleolar compartments. In hESCs, DDX18 ensures the integrity of nucleolar phase separation, which is essential for ribosome biogenesis and the regulation of pluripotency-associated genes.
Loss of DDX18 disrupts nucleolar phase separation, leading to aberrant nucleolar morphology and impaired ribosome production. This, in turn, triggers cellular stress responses and differentiation, highlighting the importance of DDX18 in preserving the unique cellular state of hESCs.
—
## DDX18