The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Accumulation of oxidative DNA damage restricts the self-renewal capacity of human hematopoietic stem cells
Open accessAbstract
Stem cells of highly regenerative organs including blood are susceptible to endogenous DNA damage caused by both intrinsic and extrinsic stress. Response mechanisms to such stress equipped in hematopoietic stem cells (HSCs) are crucial in sustaining hematopoietic homeostasis but remain largely unknown. In this study, we demonstrate that serial transplantation of human HSCs into immunodeficient mice triggers replication stress that induces incremental elevation of intracellular reactive oxygen species (ROS) levels and the accumulation of persistent DNA damage within the human HSCs. This accumulation of DNA damage is also detected in HSCs of clinical HSC transplant patients and elderly individuals. A forced increase of intracellular levels of ROS by treatment with a glutathione synthetase inhibitor aggravates the extent of DNA damage, resulting in the functional impairment of HSCs in vivo. The oxidative DNA damage activates the expression of cell-cycle inhibitors in a HSC specific manner, leading to the premature senescence among HSCs, and ultimately to the loss of stem cell function. Importantly, treatment with an antioxidant can antagonize the oxidative DNA damage and eventual HSC dysfunction. The study reveals that ROS play a causative role for DNA damage and the regulation of ROS have a major influence on human HSC aging.
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Citations
Cites
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
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Wilson, A., Laurenti, E., Oser, G., van der Wath, R. C., Blanco-Bose, W., Jaworski, M., Offner, S., Dunant, C. F., Eshkind, L., Bockamp, E., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.048 · Cited by 1,908
FoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress
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Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells
Ito, K., Hirao, A., Arai, F., Takubo, K., Matsuoka, S., Miyamoto, K., Ohmura, M., Naka, K., Hosokawa, K., Ikeda, Y., et al. (2006) · Nature Medicine · doi:10.1038/nm1388 · Cited by 1,362
Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells
Ito, K., Hirao, A., Arai, F., Matsuoka, S., Takubo, K., Hamaguchi, I., Nomiyama, K., Hosokawa, K., Sakurada, K., Nakagata, N., et al. (2004) · Nature · doi:10.1038/nature02989 · Cited by 1,175
Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age
Rossi, D. J., Bryder, D., Seita, J., Nussenzweig, A., Hoeijmakers, J., & Weissman, I. L. (2007) · Nature · doi:10.1038/nature05862 · Cited by 1,115
DNA Repair, Genome Stability, and Aging
Lombard, D. B., Chua, K. F., Mostoslavsky, R., Franco, S., Gostissa, M., & Alt, F. W. (2005) · Cell · doi:10.1016/j.cell.2005.01.028 · Cited by 944
Hematopoietic Stem Cell Quiescence Promotes Error-Prone DNA Repair and Mutagenesis
Mohrin, M., Bourke, E., Alexander, D., Warr, M. R., Barry-Holson, K., Le Beau, M. M., Morrison, C. G., & Passegué, E. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.06.014 · Cited by 599
DNA repair is limiting for haematopoietic stem cells during ageing
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DNA damage and ageing: new-age ideas for an age-old problem
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Cited by
The ageing haematopoietic stem cell compartment
Geiger, H., de Haan, G., & Florian, M. C. (2013) · Nature Reviews Immunology · doi:10.1038/nri3433 · Cited by 604
Stem cells and the impact of ROS signaling
Bigarella, C. L., Liang, R., & Ghaffari, S. (2014) · Development · doi:10.1242/dev.107086 · Cited by 632
Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells
Dykstra, B., Olthof, S., Schreuder, J., Ritsema, M., & de Haan, G. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20111490 · Cited by 494
“…the functional properties of individual HSCs gradually decline as the result of an accumulation of cellular damage such as the accrual of DNA lesions (Rossi et al., 2007a; Mohrin et al., 2010; Yahata et al., 2011) or epigenetic dysregulation (Bennett-Baker et al., 2003; Chambers et al., 2007).”
BackgroundBeerman, I., Bock, C., Garrison, B. S., Smith, Z. D., Gu, H., Meissner, A., & Rossi, D. J. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.01.017 · Cited by 485
Clonal Hematopoiesis and Evolution to Hematopoietic Malignancies
Bowman, R. L., Busque, L., & Levine, R. L. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.01.011 · Cited by 448
Metadata
- Authors
- Yahata, T., Takanashi, T., Muguruma, Y., Ibrahim, A. A., Matsuzawa, H., Uno, T., Sheng, Y., Onizuka, M., Ito, M., Kato, S., & Ando, K.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-09-15
- Volume
- 118
- Issue
- 11
- Pages
- 2941-2950
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2073692681
- Cited by
- 301
- References
- 12
- FWCI
- 15.09
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Yahata, T., Takanashi, T., Muguruma, Y., Ibrahim, A. A., Matsuzawa, H., Uno, T., Sheng, Y., Onizuka, M., Ito, M., Kato, S., & Ando, K. (2011). Accumulation of oxidative DNA damage restricts the self-renewal capacity of human hematopoietic stem cells. Blood. https://doi.org/10.1182/blood-2011-01-330050
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