Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem Cells

Sarah Rodrigues-Moreira, Stéphanie G. Moreno, Giulia Ghinatti, Daniel Lewandowski, Françoise Hoffschir, Federica Ferri, Anne Sophie Gallouet, Denise Gay, Hozumi Motohashi, Masayuki Yamamoto, Michael C. Joiner, Nathalie Gault, Paul Henri Romeo

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Despite numerous observations linking protracted exposure to low-dose (LD) radiation and leukemia occurrence, the effects of LD irradiation on hematopoietic stem cells (HSCs) remain poorly documented. Here, we show that adult HSCs are hypersensitive to LD irradiation. This hyper-radiosensitivity is dependent on an immediate increase in the levels of reactive oxygen species (ROS) that also promotes autophagy and activation of the Keap1/Nrf2 antioxidant pathway. Nrf2 activation initially protects HSCs from the detrimental effects of ROS, but protection is transient, and increased ROS levels return, promoting a long-term decrease in HSC self-renewal. In vivo, LD total body irradiation (TBI) does not decrease HSC numbers unless the HSC microenvironment is altered by an inflammatory insult. Paradoxically, such an insult, in the form of granulocyte colony-stimulating factor (G-CSF) preconditioning, followed by LD-TBI facilitates efficient bone marrow transplantation without myeloablation. Thus, LD irradiation has long-term detrimental effects on HSCs that may result in hematological malignancies, but LD-TBI may open avenues to facilitate autologous bone marrow transplantation. Rodrigues-Moreira et al. show that low-dose irradiation induces long-term oxidative stress and decreased self-renewal capacity in hematopoietic stem cells (HSCs). LD total body irradiation after an inflammatory insult decreases HSC numbers but facilitates autologous bone marrow transplantation without myeloablation.

Original languageEnglish
Pages (from-to)3199-3211
Number of pages13
JournalCell Reports
Volume20
Issue number13
DOIs
Publication statusPublished - 2017 Sep 26

Keywords

  • bone marrow transplantation
  • hematopoietic stem cell
  • low-dose irradiation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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