Low complexity domains, condensates, and stem cell pluripotency

Biological reactions require self-assembly of factors in the complex cellular milieu. Recent evidence indicates that intrinsically disordered, low-complexity sequence domains (LCDs) found in regulatory factors mediate diverse cellular processes from gene expression to DNA repair to signal transduction, by enriching specific biomolecules in membraneless compartments or hubs that may undergo liquid-liquid phase separation (LLPS). In this review, we discuss how embryonic stem cells take advantage of LCD-driven interactions to promote cell-specific transcription, DNA damage response, and DNA repair. We propose that LCD-mediated interactions play key roles in stem cell maintenance and safeguarding genome integrity.