Developmental Stage-Specific Changes in Protein Synthesis Differentially Sensitize Hematopoietic Stem Cells and Erythroid Progenitors to Impaired Ribosome Biogenesis

Adult hematopoietic stem cell (HSC) self-renewal requires precise control of protein synthesis, but fetal and adult HSCs have distinct self renewal mechanisms and lineage outputs. This raises the question of whether protein synthesis rates change with age. Here, we show that protein synthesis rates decline during HSC ontogeny, yet erythroid protein synthesis rates increase. A ribosomal mutation that impairs ribosome biogenesis (Rpl24(Bst/+)) disrupts both fetal and adult HSC self-renewal. However, the Rpl24(Bst/+) mutation selectively impairs fetal erythropoiesis at differentiation stages that exhibit fetal-specific attenuation of protein synthesis. Developmental changes in protein synthesis thus differentially sensitize hematopoietic stem and progenitor cells to impaired ribosome biogenesis.

Automated summary

This study found that protein synthesis rates decrease during HSC ontogeny, while erythroid protein synthesis rates increase. A ribosomal mutation impacting ribosome biogenesis can disrupt HSC self-renewal, particularly in fetal erythropoiesis. Developmental changes in protein synthesis cause hematopoietic stem and progenitor cells to have differential sensitivity to impaired ribosome biogenesis.