A protein synthesis brake for hematopoietic stem cell maintenance.

Bmi1 is essential for normal and leukemic hematopoiesis, but its target genes in hematopoietic stem cells (HSCs) are incompletely understood. In this issue of , Burgess et al. (pp. 887-900) demonstrate a novel role of Bmi1 in regulating ribosome biogenesis and protein synthesis. -deficient HSCs exhibited reduced transplantability, with the up-regulation of ARX and genes involved in ribosome biogenesis. However, depletion of or its known targets, , only partially rescues loss-induced hematopoietic defects. They further demonstrate an increased protein synthesis rate and resultant proteostatic stress in HSCs, indicating a novel mechanism by which Bmi1 controls HSC maintenance.