Liquid-liquid phase separation (LLPS), a novel mechanism of the organization and formation of cellular structures, plays a vital role in regulating cell fate transitions and disease pathogenesis and is gaining widespread attention. LLPS may lead to the assemblage of cellular structures with liquid-like fluidity, such as germ granules, stress granules, and nucleoli, which are classic membraneless organelles. These structures are typically formed through the high-concentration liquid aggregation of biomacromolecules driven by weak multivalent interactions. LLPS is involved in regulating various intracellular life activities and its dysregulation may cause the disruption of cellular functions, thereby contributing to the pathogenesis and development of neurodegenerative diseases, infectious diseases, cancers, etc. Herein, we summarized published findings on the LLPS dynamics of membraneless organelles in physiological and pathological cell fate transition, revealing their crucial roles in cell differentiation, development, and various pathogenic processes. This paper provides a fresh theoretical framework and potential therapeutic targets for LLPS-related studies, opening new avenues for future research.
液-液相分离作为一种细胞结构的组织与形成的新机制，在调控细胞命运转变和疾病发病机制中发挥着重要作用，正受到广泛关注。液-液相分离可形成一些具有液态流动性的细胞结构，如生殖颗粒、压力应激颗粒和核仁等经典的无膜细胞器，它们通常由生物大分子通过弱的多价相互作用形成的高浓度液体聚集而来。液-液相分离可参与调节细胞内的多种生命活动，其异常则会导致细胞功能紊乱，从而促进神经退行性疾病、传染病及癌症等疾病的发生发展。本综述通过总结各种无膜细胞器在生理与病理性细胞命运转变过程中的液-液相分离动态，揭示了它们在细胞分化、发育及各种疾病发生过程中的关键作用，为液-液相分离相关研究提供了新的理论框架和潜在的疾病治疗靶点，为未来的研究提供了新的方向。
Keywords: Cell fate transition; Disease pathogenesis; Phase separation; Review; Therapeutics.
Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).