On Nov. 9th, 2021, Hua Yu et.al from Dr. Jin Zhang’s grouppublished rRNAbiogenesis regulates mouse 2C-like state by 3D structure reorganization ofperi-nucleolar heterochromatin at NatureCommunications.

The nucleolus is the organelle for ribosomebiogenesis and sensing various types of stress. However, its role in regulatingstem cell fate remains unclear. Here, we present evidence that nucleolar stressinduced by interfering rRNA biogenesis can drive the 2-cell stage embryolike(2C-like) program and induce an expanded 2C-like cell population in mouseembryonic stem (mES) cells. Mechanistically, nucleolar integrity maintainsnormal liquid-liquid phase separation (LLPS) of the nucleolus and the formationof peri-nucleolar heterochromatin (PNH). Upon defects in rRNA biogenesis, thenatural state of nucleolus LLPS is disrupted, causing dissociation of theNCL/TRIM28 complex from PNH and changes in epigenetic state and reorganizationof the 3D structure of PNH, which leads to release of Dux, a 2C programtranscription factor, from PNH to activate a 2C-like program. Correspondingly,embryos with rRNA biogenesis defect are unable to develop from 2-cell (2C) to 4-cellembryos, with delayed repression of 2C/ERV genes and a transcriptome skewedtoward earlier cleavage embryo signatures. Our results highlight thatrRNA-mediated nucleolar integrity and 3D structure reshaping of the PNHcompartment regulates the fate transition of mES cells to 2Clike cells, andthat rRNA biogenesis is a critical regulator during the 2-cell to 4-celltransition of murine pre-implantation embryo development.