Rbpms represses translation elongation to maintain adult hematopoietic stem cell quiescence (PRJCA036589)

The mechanisms by which hematopoietic stem cells (HSCs) maintain long-term hematopoietic capacity and transition from a quiescent to an activated state are unknown, which severely limits their in vitro expansions and clinical applications. In recent years, several reports have indicated that maintaining a low protein synthesis rate in HSCs is the most important, but the underlined mechanism has been unknown for a long time. In this study, we identified a series of ribosome associated proteins in HSCs and found that RNA-binding protein-Rbpms was required for maintaining low protein synthesis rate in HSCs. The deletion of Rbpms led to accelerated protein synthesis and accumulation of unfolded and misfolded proteins in HSCs, which severely impaired their long-term hematopoietic reconstitution capacity and resulted in their aberrant exit from the quiescent state. The mechanism study showed that Rbpms can undergo liquid-liquid phase separation in vitro and formed membrane-less organelles in HSCs, sequestering translation elongation factor Eef1a1 and its chaperones from ribosomes in the translation, to maintain the low translation elongation rate to guarantee the elegant protein folding in HSCs. This work highlights the pivotal role of translation control and membrane-less organelles in HSCs function.