An adaptive phase transition in GC is responsible for nucleoli reorganization upon nucleolar stress

The nucleolus is a membrane-less organelle formed through molecular mechanism of liquid-liquid phase separation of its components from the surrounding nucleoplasm. Nucleolar stress in cancer or tumor cells had been well studied, but the dynamic reorganization process and its molecular and cellular mechanisms involved in phase transition of nucleoli in mouse embryonic stem cells had not been elucidated. Herein, we generate a nucleoli reorganization model in mESCs via a small chemical CX induced inhibitory rRNA biogenesis. We depicted critical nucleolar components repartition upon stress, companied with phase transition in granular component (GC). We suggest the segregation of dense fibrillary component (DFC) is responsible for more liquid-like phase transition in GC, except for the suspicion of lower cellular salt concentration and/or accumulated rRNA induced by CX, which is verified by GC protein NPM1 phase diagram in vitro. Administration of HEX conducts nucleoli an alternative phase transition under stress. Non-physiological GC protein accumulation and interfered hydrophobic microenvironment by HEX contribute its assembles curing and over-condensation in vitro, leading to solid-like phase transition of GC in HEX-plus CX mESCs.