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.
Keywords: polycomb; self-renewal; senescence; tissue regeneration; tumor suppressor.
© 2022 Lv and Tong; Published by Cold Spring Harbor Laboratory Press.