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

Jeffrey A. Magee, Robert A.J. Signer

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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 (Rpl24Bst/+) disrupts both fetal and adult HSC self-renewal. However, the Rpl24Bst/+ 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.

Original languageEnglish
Pages (from-to)20-28
Number of pages9
JournalStem Cell Reports
Volume16
Issue number1
DOIs
StatePublished - Jan 12 2021

Keywords

  • erythroid
  • erythropoiesis
  • hematopoiesis
  • hematopoietic stem cell
  • progenitor
  • protein synthesis
  • proteostasis
  • ribosome
  • ribosomopathy
  • translation

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