Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem Cells
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-09-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717312743 |
| _version_ | 1819043511114137600 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sarah Rodrigues-Moreira |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T09:57:56Z |
| format | Article |
| id | doaj.art-a4f6171576b143b79c56642349f898f3 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T09:57:56Z |
| publishDate | 2017-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a4f6171576b143b79c56642349f898f32022-12-21T19:08:00ZengElsevierCell Reports2211-12472017-09-0120133199321110.1016/j.celrep.2017.09.013Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem CellsSarah Rodrigues-Moreira0Stéphanie G. Moreno1Giulia Ghinatti2Daniel Lewandowski3Françoise Hoffschir4Federica Ferri5Anne-Sophie Gallouet6Denise Gay7Hozumi Motohashi8Masayuki Yamamoto9Michael C. Joiner10Nathalie Gault11Paul-Henri Romeo12CEA/DRF/IBFJ/iRCM/LRTS, 92265 Fontenay-aux-Roses Cedex, FranceCEA/DRF/IBFJ/iRCM/LRTS, 92265 Fontenay-aux-Roses Cedex, FranceCEA/DRF/IBFJ/iRCM/LRTS, 92265 Fontenay-aux-Roses Cedex, FranceCEA/DRF/IBFJ/iRCM/LRTS, 92265 Fontenay-aux-Roses Cedex, FranceCEA/DRF/IBFJ/iRCM/LRTS, 92265 Fontenay-aux-Roses Cedex, FranceCEA/DRF/IBFJ/iRCM/LRTS, 92265 Fontenay-aux-Roses Cedex, FranceCEA/DRF/IBFJ/iRCM/LRTS, 92265 Fontenay-aux-Roses Cedex, FranceCEA/DRF/IBFJ/iRCM/LRTS, 92265 Fontenay-aux-Roses Cedex, FranceDepartment of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, JapanDepartment of Medical Biochemistry, Graduate School of Medicine, Tohoku University, Sendai, JapanWayne State University School of Medicine, Detroit, MI 48201, USACEA/DRF/IBFJ/iRCM/LRTS, 92265 Fontenay-aux-Roses Cedex, FranceCEA/DRF/IBFJ/iRCM/LRTS, 92265 Fontenay-aux-Roses Cedex, FranceDespite 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.http://www.sciencedirect.com/science/article/pii/S2211124717312743low-dose irradiationhematopoietic stem cellbone marrow transplantation |
| spellingShingle | 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 Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem Cells Cell Reports low-dose irradiation hematopoietic stem cell bone marrow transplantation |
| title | Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem Cells |
| title_full | Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem Cells |
| title_fullStr | Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem Cells |
| title_full_unstemmed | Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem Cells |
| title_short | Low-Dose Irradiation Promotes Persistent Oxidative Stress and Decreases Self-Renewal in Hematopoietic Stem Cells |
| title_sort | low dose irradiation promotes persistent oxidative stress and decreases self renewal in hematopoietic stem cells |
| topic | low-dose irradiation hematopoietic stem cell bone marrow transplantation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717312743 |
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