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 Genes & Development, Burgess et al. (pp. 887–900) demonstrate a novel role of Bmi1 in regulating ribosome biogenesis and protein synthesis. Bmi1-deficient HSCs exhibited reduced transplantability, with the up-regulation of ARX and genes involved in ribosome biogenesis. However, depletion of ARX or its known targets, p16(Ink4a)/p19(Arf), only partially rescues Bmi1 loss-induced hematopoietic defects. They further demonstrate an increased protein synthesis rate and resultant proteostatic stress in Bmi1(−/−) HSCs, indicating a novel mechanism by which Bmi1 controls HSC maintenance.