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

研究成果: Article査読

42 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)3199-3211
ページ数13
ジャーナルCell Reports
20
13
DOI
出版ステータスPublished - 2017 9 26

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)

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