The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells
Abstract
The 'ataxia telangiectasia mutated' (Atm) gene maintains genomic stability by activating a key cell-cycle checkpoint in response to DNA damage, telomeric instability or oxidative stress. Mutational inactivation of the gene causes an autosomal recessive disorder, ataxia-telangiectasia, characterized by immunodeficiency, progressive cerebellar ataxia, oculocutaneous telangiectasia, defective spermatogenesis, premature ageing and a high incidence of lymphoma. Here we show that ATM has an essential function in the reconstitutive capacity of haematopoietic stem cells (HSCs) but is not as important for the proliferation or differentiation of progenitors, in a telomere-independent manner. Atm-/- mice older than 24 weeks showed progressive bone marrow failure resulting from a defect in HSC function that was associated with elevated reactive oxygen species. Treatment with anti-oxidative agents restored the reconstitutive capacity of Atm-/- HSCs, resulting in the prevention of bone marrow failure. Activation of the p16(INK4a)-retinoblastoma (Rb) gene product pathway in response to elevated reactive oxygen species led to the failure of Atm-/- HSCs. These results show that the self-renewal capacity of HSCs depends on ATM-mediated inhibition of oxidative stress.
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In the citing paper
“other studies have shown the potential of antioxidants to improve the function of old HSCs (76,96).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [96]
In the citing paper
“in HSCs and neural stem cells (NSCs) of mice, excessive cellular ROS concentrations lead to abnormal proliferation, malignancy and compromised stem cell self-renewal11–14”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [11]
In the citing paper
“experimentally induced genetic disruption of DDR pathways in mice also produces cell-autonomous defects in HSC function, as assayed by in vivo hematopoietic reconstitution and in vitro colony forming assays11,36,52,53.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [11]
In the citing paper
“age-dependent alterations in regulation of SOD2 by FoxO3 and the DNA damage sensing serine/threonine protein kinase ATM (ataxia-telangiectasia mutated) have been shown to contribute to loss of HSC function with aging11,16, 24.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [11]
In the citing paper
“Another potential function for ATM in suppressing progeroid phenotypes may be related to reported ATM functions in regulating intracellular ROS levels and sensitivity to these molecules (Barzilai et al., 2002; Ito et al., 2004”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Ito et al., 2004
In the citing paper
“Inactivation of the p16-Rb pathway restores the reproductive function of ATM−/− HSCs, whereas inhibition of the Arf-p53 pathway has no such effect.20,21”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [20]
In the citing paper
“Furthermore, mutation of the ataxia telangiectasia mutated (ATM) gene also results in upregulation of p16 and Arf in HSCs.”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [20]
In the citing paper
“ROS plays an important role in mediating induction of HSC senescence under various pathological conditions, such as mutation of ATM and various Fanconi anemia genes; deletion of Bmi1, FoxOs, Mdm2, and Tsc1; and aging.15,19,20,35-38”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [20]
In the citing paper
“mice lacking Atm show rapid ageing and depletion of their haematopoietic stem cell compartment 34”
From The common biology of cancer and ageing (2007) · cites this paper as [34]
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Cited by
Sorted by citations
Items 701–800 of 1,000
All Stressed Out Without ATM Kinase
Perry, J. J. P., & Tainer, J. A. (2011) · Science Signaling · doi:10.1126/scisignal.2001961 · Cited by 22
“Although an A-T–like neuropathology is absent in ATM mice, these mice exhibit bone marrow failure that is linked to excessive ROS occurs and that can be ameliorated through the use of antioxidants (21).”
BackgroundKuang, X., Yan, M., Ajmo, J. M., Scofield, V. L., Stoica, G., & Wong, P. K. Y. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.01.008 · Cited by 22
Yin, L., & Kufe, D. W. (2011) · Genes & Cancer · doi:10.1177/1947601911405044 · Cited by 22
“The finding that ataxia telangiectasia mutated (ATM)–deficient mice develop bone marrow failure that is reversed by NAC provided one link between redox imbalance and loss of hematopoietic cell self-renewal.(46) Other studies have shown that FOXO family members protect against oxidative stress and that FOXO-deficient m…”
BackgroundCardiac Stem Cells: Biology and Clinical Applications
Goichberg, P., Chang, J., Liao, R., & Leri, A. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.5875 · Cited by 24
“In this regard, if the rise in cellular ROS is not well adjusted, as in the case of the genetic ablation of the ATM or FoxO proteins, the self-renewal capacity and differentiation pattern of hematopoietic stem cells are severely compromised (55, 100, 149, 164, 165).”
BackgroundRejuvenating Aged Hematopoietic Stem Cells Through Improvement of Mitochondrial Function
Moon, J., Kim, H. R., & Shin, M. (2018) · Annals of Laboratory Medicine · doi:10.3343/alm.2018.38.5.395 · Cited by 24
The effects of Nrf2 knockout on regulation of benzene-induced mouse hematotoxicity
Li, H., Li, D., He, Z., Fan, J., Li, Q., Liu, X., Guo, P., Zhang, H., Chen, S., Li, Q., et al. (2018) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2018.09.002 · Cited by 22
Ferreira, A. C., Sousa, N., Bessa, J. M., Sousa, J. C., & Marques, F. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.014 · Cited by 24
Lam, Y. T. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/7095901 · Cited by 22
“Mice with Atm deficiency (Atm−/−) exhibit progressive bone marrow failure in association with increased ROS levels [99].”
BackgroundATM activation by a sulfhydryl‐reactive inflammatory cyclopentenone prostaglandin
Kobayashi, M., Ono, H., Mihara, K. L., Tauchi, H., Komatsu, K., Shibata, T., Shimizu, H., Uchida, K., & Yamamoto, K. (2006) · Genes to Cells · doi:10.1111/j.1365-2443.2006.00976.x · Cited by 22
“More recently, impaired self-renewal of hematopoietic stem cells in ATM knockout mice has been attributed to the defective response to oxidative stress (Ito et al., 2004).”
BackgroundMontoya, B., Valverde, M., Rojas, E., & Torres, R. (2016) · Journal of Experimental Biology · doi:10.1242/jeb.141325 · Cited by 22
“There is evidence that some components of oxidative balance have a genetic basis (e.g. antioxidant enzymes, Ito et al., 2004; resistance of red blood cells to haemolysis, Kim et al., 2010).”
BackgroundThe role of immune cells settled in the bone marrow on adult hematopoietic stem cells
Xu, H., Li, Y., & Gao, Y. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05445-3 · Cited by 22
“Consequently, the niche requires a hypoxic environment to sustain the quiescent state of HSCs, thereby avoiding stem cell exhaustion and preserving their long-term regenerative capacity [ 171–173 ].”
BackgroundLalioti, M., Romero-Mulero, M. C., Karabacz, N., Mess, J., Demollin, H., Rettkowski, J., Schuldes, K., Mitterer, M., Wadle, C., Shoumariyeh, K., et al. (2025) · Nature Cell Biology · doi:10.1038/s41556-025-01709-7 · Cited by 21
“1f–i and Supplementary Table 4), suggesting that HSPCs are overall metabolically less active than their downstream progenitors, consistent with previous studies performed in mice 25–28 .”
Managing odds in stem cells: insights into the role of mitochondrial antioxidant enzyme MnSOD
Sheshadri, P., & Kumar, A. (2016) · Free Radical Research · doi:10.3109/10715762.2016.1155708 · Cited by 21
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“ROS has also been demonstrated to prime the differentiation of hematopoietic progenitors in Drosophila, [47] and the disturbance in oxidative/anti-oxidative system leads to premature HSC senescence due to loss of quiescence and self-renewal capacity in HSCs of mouse models [47, 48].”
BackgroundJakubison, B. L., Sarkar, T., Gudmundsson, K. O., Singh, S., Sun, L., Morris, H. M., Klarmann, K. D., & Keller, J. R. (2022) · Journal of Clinical Investigation · doi:10.1172/jci152599 · Cited by 21
ROR2 regulates self-renewal and maintenance of hair follicle stem cells
Veltri, A., Lang, C. M. R., Cangiotti, G., Chan, C. K., & Lien, W. (2022) · Nature Communications · doi:10.1038/s41467-022-32239-7 · Cited by 22
Understanding chronic neutropenia: life is short
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MUC1-C oncoprotein promotes FLT3 receptor activation in acute myeloid leukemia cells
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ATM in focus: A damage sensor and cancer target
Khalil, H. S., Tummala, H., & Zhelev, N. (2012) · Biodiscovery · doi:10.7750/biodiscovery.2012.5.1 · Cited by 23
“In keeping with ATM’s role in oxidative stress, further studies showed that the phenotypic abnormalities seen in ATM null cell lines could be rescued by the addition of antioxidants, thus demonstrating that at least a part of the cellular defects seen in ATM null genotypes are because of accumulation of oxidative dama…”
Premeiotic germ cell defect in seminiferous tubules of Atm-null testis
Takubo, K., Hirao, A., Ohmura, M., Azuma, M., Arai, F., Nagamatsu, G., & Suda, T. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.145 · Cited by 21
Self-citationMitochondria underlie different metabolism of hematopoietic stem and progenitor cells
Arranz, L., Urbano-Ispizúa, Á., & Méndez‐Ferrer, S. (2013) · Haematologica · doi:10.3324/haematol.2013.084293 · Cited by 26
“HSC deficient in ATM exhibit increased ROS levels and reduced self-renewal.(14) In addition, the Foxhead O (FoxO) subfamily of transcription factors regulates ATM expression and ROS levels in HSC, since deletion of FoxO1,3 and 4 resulted in increased ROS production and decreased HSC self-renewal.”
BackgroundInfluentialKaneyuki, Y., Yoshino, H., & Kashiwakura, I. (2012) · Journal of Radiation Research · doi:10.1269/jrr.11099 · Cited by 21
Stem cell state and the epithelial-to-mesenchymal transition: Implications for cancer therapy
Donnenberg, V. S., & Donnenberg, A. D. (2015) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.486 · Cited by 19
“self-renewal.(32) Regulation of ROS is mediated by the FoxO family of transcription factors, which induce manganese superoxide dismutase, a potent and highly conserved ROS scavenger.”
BackgroundATM, DNA-PKcs and ATR: shaping development through the regulation of the DNA damage responses
Menolfi, D., & Zha, S. (2019) · Genome Instability & Disease · doi:10.1007/s42764-019-00003-9 · Cited by 21
Duecker, R. P., Baer, P. C., Buecker, A., Huenecke, S., Pfeffermann, L., Modlich, U., Bakhtiar, S., Bader, P., Zielen, S., & Schubert, R. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02785 · Cited by 20
“Due to the ATM deficiency and the impaired reparation of DNA strand breaks, oxidative stress in hematopoietic stem cells accumulates, and the hematopoietic stem cells lose the ability to self-renew (20, 21, 37).”
BackgroundZhao, Z., Gao, J., Li, C., Xu, X., Hu, Y., & Huang, S. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/1621687 · Cited by 20
“Accordingly, increasing the ROS level in hematopoietic stem cells by knockout the gene of Atm or FoxOmay promote the differentiation of hematopoietic stem cells [20, 21].”
BackgroundHuff, L. A., Yan, S., & Clemens, M. G. (2021) · Antioxidants · doi:10.3390/antiox10071146 · Cited by 21
“A-T is characterized by accumulation of RONS [94,95], high oxidative stress, loss of hematopoietic stem cells, premature aging, immunodeficiency, extreme sensitivity to ionizing radiation, chromosomal instability, defective spermatogenesis, and increased risk for certain cancers, especially lymphoid cancers [34,96].”
BackgroundLife-history Constraints on the Mechanisms that Control the Rate of ROS Production
Aledo, J. C. (2014) · Current Genomics · doi:10.2174/1389202915666140515230615 · Cited by 20
“Evidences also point to a connection between mitochondrial ROS and stem cell function [26, 27], insulin signalling [28, 29], senescence”
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Gault, N., Verbiest, T., Badie, C., Roméo, P., & Bouffler, S. D. (2019) · International Journal of Radiation Biology · doi:10.1080/09553002.2019.1569777 · Cited by 20
“…mice deficient for the atm or foxo3a genes have shown that high levels of ROS in HSCs are associated with numerous alterations of their functions and that NAC pretreatment can rescue the phenotype of HSCs pinpointing a direct role of ROS in these phenotypes (Ito et al. 2004; Miyamoto et al. 2007).”
BackgroundPhotoactivated cell-killing involving a low molecular weight, donor–acceptor diphenylacetylene
Chisholm, D. R., Lamb, R., Pallett, T. L., Affleck, V., Holden, C. A., Marrison, J., O’Toole, P. J., Ashton, P. D., Newling, K., Steffen, A., et al. (2019) · Chemical Science · doi:10.1039/c9sc00199a · Cited by 20
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“Interestingly, 3D-neurosphere forming ability is severely impaired in ATM:KO cells, a feature that would concur with a previous study demonstrating a role for ATM in the re-constitutive capacity of haematopoetic stem cells [51].”
BackgroundModerate Static Magnet Fields Suppress Ovarian Cancer Metastasis via ROS‐Mediated Oxidative Stress
Song, C., Yu, B., Wang, J., Ji, X., Zhang, L., Tian, X., Yu, X., Feng, C., Wang, X., & Zhang, X. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/7103345 · Cited by 20
“to be critical for the self-renewal of stem cells [22, 23].”
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Niculescu, V. F. (2015) · Stem Cell Biology and Research · doi:10.7243/2054-717x-2-2 · Cited by 23
The role of vascular stem cells in atherogenesis and post-angioplasty restenosis
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Copper Modulates the Differentiation of Mouse Hematopoietic Progenitor Cells in Culture
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Elevated Oxidative Stress Impairs Hematopoietic Progenitor Function in C57BL/6 Substrains
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“, 2006), self-renewal (Ito et al., 2004; Le et al., 2016), and differentiation (Cao et al.”
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A Radical Bailout Strategy for Cancer Stem Cells
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“Furthermore, the demise of these mutant HSCs can be reverted by in vivo antioxidant therapy (Ito et al., 2004; Miyamoto et al., 2007; Tothova et al., 2007), indicating a causal link between ROS and HSC longevity.”
BackgroundFancd2 Is Required for Nuclear Retention of Foxo3a in Hematopoietic Stem Cell Maintenance
Li, X., Li, J., Wilson, A., Sipple, J., Schick, J. S., & Pang, Q. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.619536 · Cited by 19
“Studies in ATM (ataxia telangiectasia mutated) deficient mice showed progressive BM failure resulting from a defect in HSC function that was associated with elevated reactive oxygen species that induce oxidative stress (7).”
BackgroundThe role of PML in hematopoietic and leukemic stem cell maintenance
Nakahara, F., Weiss, C. N., & Ito, K. (2014) · International Journal of Hematology · doi:10.1007/s12185-014-1518-x · Cited by 18
“HSCs are particularly vulnerable to the effects of oxidative stress, especially DNA damage, due to their longevity [17, 25, 26], and the ability of HSCs to self-renew”
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Reactive Oxygen Species as Signaling Molecules
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“Nonetheless, some animals do not develop tumors and in this context it was observed that cancer-free Atm –/– mice at 6 months started to develop a picture of bone marrow failure [ 40 ].”
BackgroundThioredoxin-interacting protein, hematopoietic stem cells, and hematopoiesis
Jung, H., & Choi, I. (2014) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000037 · Cited by 19
“function, a function that was associated with elevated ROS [56].”
BackgroundStem cell exhaustion and leukemogenesis
Jacob, B., & Osato, M. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22150 · Cited by 19
DNA damage response, redox status and hematopoiesis
Weiss, C. N., & Ito, K. (2013) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2013.08.002 · Cited by 19
“Finally, Gross and Korsmeyer observed increased levels of p16INK4A and p19ARF expression in BidAA mice, consistent with studies of Atm−/− mice [46; 70].”
BackgroundResultInfluentialSelf-citationCited2 in hematopoietic stem cell function
Du, J., & Yang, Y. (2013) · Current Opinion in Hematology · doi:10.1097/moh.0b013e3283606022 · Cited by 19
Regulation of Hematopoietic Stem Cells in the Osteoblastic Niche
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Self-citationAutophagy in Myocardial Differentiation and Cardiac Development
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Singh, A. K., Prasad, P., & Cancelas, J. A. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1325291 · Cited by 21
“Mitochondria are the major source of cellular bioenergetics and an important regulator of HSC fate decisions and energy homeostasis (Ito et al., 2004; Liu et al., 2015; Ito et al., 2016; Khacho et al., 2016; Luchsinger et al., 2016; Hu et al., 2018; Jin et al., 2018; Umemoto et al., 2018; Hinge et…”
BackgroundVlaski‐Lafarge, M., & Ivanović, Z. (2015) · Journal of Cell Science · doi:10.1242/jcs.171496 · Cited by 19
“Because all these probes allow analysis at single-cell level by flow cytometry, we propose the following procedure to measure ROS and RNS in LSK cell populations that contain HSCs and HPCs (Fig.”
BackgroundResultInfluentialJMJD6 promotes self-renewal and regenerative capacity of hematopoietic stem cells
Lawson, H., Sepúlveda, C., van de Lagemaat, L. N., Durko, J., Barile, M., Tavosanis, A., Georges, E., Shmakova, A., Timms, P., Carter, R. N., et al. (2021) · Blood Advances · doi:10.1182/bloodadvances.2020002702 · Cited by 18
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Energy Producing Metabolic Pathways in Functional Regulation of the Hematopoietic Stem Cells
Roy, I. M., Biswas, A., Verfaillie, C. M., & Khurana, S. (2018) · IUBMB Life · doi:10.1002/iub.1870 · Cited by 18
“Deletion of Ataxia telangiectasia mutated (Atm) gene, one such checkpoint regulator, leads to increased ROS accumulation in the HSCs and start showing bone marrow failure in as early as 24 weeks (43).”
BackgroundGu, C., Gonzalez, J., Zhang, T., Kamel‐Reid, S., & Wells, R. A. (2013) · Leukemia Research · doi:10.1016/j.leukres.2013.10.010 · Cited by 18
Activating p53 abolishes self-renewal of quiescent leukaemic stem cells in residual CML disease
Scott, M. T., Liu, W., Mitchell, R., Clarke, C. J., Kinstrie, R., Warren, F., Almasoudi, H. H., Stevens, T., Dunn, K. M., Pritchard, J., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-44771-9 · Cited by 20
“To explore the signi fi cance of these ES-related signatures,weexaminedthemeanmRNAlevelofeachsignatureacross19 clustersof peripheral blood derived CD34 + CD38 − HSC or LSC obtained from single cell RNA-sequencing (scRNA-seq) (Supplementary Fig.”
InfluentialChen, K., Li, Y., Wu, X., Tang, X., Zhang, B., Fan, T., He, L., Pei, X., & Li, Y. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03743-y · Cited by 18
“As ROS are known to be involved in hematopoietic injury [51–53], it would be meaningful to further investigate the dynamic change of ROS in different types of hematopoietic and niche cells in the organoids after radiation.”
BackgroundCharitou, P., & Burgering, B. M. T. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4921 · Cited by 17
“More specifically, ATM - / - mice exhibit depletion of their HSC pool and bone marrow failure due to elevated ROS, whereas the HSC defects are relieved with concomitant administration of NAC (79).”
Kwon, T.-H., Han, Y., Hong, S. G., Lee, D. J., Ha, H., Kang, S. W., Li, W. S., Yoon, D. Y., & Yu, D. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.06.113 · Cited by 18
Khan, N., Hills, R. K., Knapper, S., Steadman, L. G., Qureshi, U., Rector, J. L., Bradbury, C. A., Russell, N. H., Vyas, P., Burnett, A. K., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0163291 · Cited by 17
Machida, K. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7241 · Cited by 18
“As another example, disruption of ATM promotes ROS production and leads to stem cell depletion (22).”
BackgroundAllicin alleviates lead-induced hematopoietic stem cell aging by up-regulating PKM2
Cai, S., Zhao, L., Liu, J., Ji, Y., Shi, X., Ma, Z.-R., Lv, X., Chen, K., & Chen, Y. (2019) · Bioscience Reports · doi:10.1042/bsr20190243 · Cited by 17
Mitochondria Turnover and Lysosomal Function in Hematopoietic Stem Cell Metabolism
Mochizuki‐Kashio, M., Shiozaki, H., Suda, T., & Nakamura‐Ishizu, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094627 · Cited by 19
“In order to reduce ROS-associated cellular damage, ROS production is minimized through the suppression of OXPHOS in HSCs [6,26].”
BackgroundSelf-citationRb and hematopoiesis: stem cells to anemia
Walkley, C. R., Sankaran, V. G., & Orkin, S. H. (2008) · Cell Division · doi:10.1186/1747-1028-3-13 · Cited by 18
“The "Rb pathway" has also been implicated in phenotypes observed in both the Bmi1-/- and ATM-/- HSCs [48-50].”
Gladdy, R. A., Nutter, L. M. J., Kunath, T., Danska, J. S., & Guidos, C. J. (2006) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-05-0258 · Cited by 17
“accumulation of reactive oxygen species (27).”
The Mef/Elf4 Transcription Factor Fine Tunes the DNA Damage Response
Sashida, G., Bae, N., Giandomenico, S. D., Asai, T., Gurvich, N., Bazzoli, E., Liu, Y., Huang, G., Zhao, X., Menéndez, S., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-0455 · Cited by 17
“The absence of ATM, or an overactive ATM kinase, leads to HSC exhaustion and depletion over time (15, 16).”
BackgroundWang, H., Yang, Y., Zhang, H., Yan, H., Wu, X., & Zhang, C. (2014) · BioMed Research International · doi:10.1155/2014/282657 · Cited by 17
“Several recent studies have also demonstrated that the induction of oxidative stress is primarily responsible for the loss of HSC self-renewal as well as the premature exhaustion of HSCs in mice that have mutations in the ATM [10] and deletion of FoxO3(s) [11].”
BackgroundDong, C., Wang, X., Sun, L., Zhu, L., Yang, D., Gao, S., Zhang, W., Ling, B., Liang, A., Gao, Z., et al. (2022) · Stem Cell Research · doi:10.1016/j.scr.2021.102618 · Cited by 16
Rossin, D., Perrelli, M.-G., Iacono, M. L., Rastaldo, R., & Giachino, C. (2025) · Antioxidants · doi:10.3390/antiox14060691 · Cited by 20
“Maintaining low ROS levels, regulated by both internal and external factors, is crucial for stem cell self-renewal, migration, development, and cell cycle regulation [83–85].”
Inflammation and hematopoietic stem cells aging
He, H., & Wang, J. (2020) · Blood Science · doi:10.1097/bs9.0000000000000063 · Cited by 16
Genomic landscape of liquid biopsy mutations in TP53 and DNA damage genes in cancer patients
Vasseur, D., Arbab, A., Giudici, F., Marzac, C., Michiels, S., Tagliamento, M., Bayle, A., Smolenschi, C., Sakkal, M., Aldea, M. D., et al. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00544-7 · Cited by 18
“The ATM gene has been described as a key element in the reconstitution of HSC capacity, a non-functional gene leading to increased reactive oxygen species and bone narrow failure 22 .”
Cardiac Nonmyocyte Cell Functions and Crosstalks in Response to Cardiotoxic Drugs
Gambardella, J., Trimarco, B., Iaccarino, G., & Sorriento, D. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/1089359 · Cited by 17
“ATM is a kinase that is recruited and activated in response to oxidative stressinduced DNA damage [52].”
BackgroundChoi, J. E., & Chung, W. (2019) · The Journal of Microbiology · doi:10.1007/s12275-020-9520-x · Cited by 17
Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem Cells
Li, Y., He, M. T., Zhang, W., Yang, M., Ding, Y., Xu, S., Gu, J., Li, Y., Yin, J., & Gao, Y. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00399 · Cited by 16
“, 2004), and activate pathways that may lead to self-renewal defects such as p38 MAPK, mTOR, and more (Ito et al., 2004; Ito et al., 2006; Yoshida et al., 2011).”
BackgroundStressed marrow: FoxOs stem tumour growth
Coffer, P. J., & Burgering, B. M. T. (2007) · Nature Cell Biology · doi:10.1038/ncb0307-251 · Cited by 16
Radbruch, H., Mothes, R., Bremer, D., Seifert, S., Köhler, R., Pohlan, J., Ostendorf, L., Günther, R., Leben, R., Stenzel, W., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00844 · Cited by 15
“Immunosenescence is a multifactorial phenomenon caused, among other factors, by the diminished potential of hematopoietic stem cells to self-renew (24), agedependent impairment of antigen-presenting cells (25), a reduction of T cell (26) and B cell repertoire and numbers (27), causing a decline in adaptive immunity (2…”
BackgroundMicroRNA-127-3p controls murine hematopoietic stem cell maintenance by limiting differentiation
Crisafulli, L., Muggeo, S., Uva, P., Wang, Y., 岩崎, 正., Locatelli, S. L., Anselmo, A., Colombo, F., Carlo‐Stella, C., Cleary, M. L., et al. (2019) · Haematologica · doi:10.3324/haematol.2018.198499 · Cited by 16
“Since oxidative stress has been described to negatively affect HSC function, we measured reactive oxygen species (ROS) production in response to cytokine stimulation, as described.(23) ROS production induced upon short in vitro cytokine exposure was similar in HSC within Lincells isolated from 127DR or EV recipients (…”
BackgroundTeng, E. C., Todd, L. R., Ribar, T. J., Lento, W. E., DiMascio, L. N., Means, A. R., & Sankar, U. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e10-08-0723 · Cited by 17
Stem cell aging: what bleach can teach
Liu, J., & Finkel, T. (2006) · Nature Medicine · doi:10.1038/nm0406-383 · Cited by 16
Genome Damage Sensing Leads to Tissue Homeostasis in Drosophila
Khan, C., Muliyil, S., & Rao, B. J. (2019) · International review of cytology · doi:10.1016/bs.ircmb.2018.12.001 · Cited by 15
Fu, S., Hu, J., Chen, X., Li, B., Shun, H., Deng, J., Zhang, Y., Yao, Y., & Zhao, Y. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.658908 · Cited by 15
“456 Pulmonary artery diameter (mm) 21 (20, 23) 22 (20, 23) 21 (20, 23) 0.”
BackgroundSuzuki, K., Imaoka, T., Tomita, M., Sasatani, M., Doi, K., Tanaka, S., Kai, M., Yamada, Y., & Kakinuma, S. (2023) · Journal of Radiation Research · doi:10.1093/jrr/rrad003 · Cited by 16
“[42] first reported that ATM serves essential roles in the reconstitutive capacity of HSCs but is not important for the proliferation or differentiation of progenitors, in a telomere-independent manner in mice.”
BackgroundMitochondria Dictate Function and Fate of HSCs and T Cells
Xu, Y., Chiang, Y.-H., Ho, P., & Vannini, N. (2023) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-22-0685 · Cited by 16
Asgari, R., Mehran, Y. Z., Weber, H. M., Weber, M., Golestanha, S. A., Kazerouni, S. M. H., Panahi, F., Mohammadi, P., & Mansouri, K. (2024) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2024.106715 · Cited by 17
Taylor, D., Wilkison, M., Voyich, J. M., & Meissner, N. N. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003558 · Cited by 15
“ROS production has been shown to induce apoptotic cell death in neutrophils (32, 33) and is causally linked to the development of progressive BM failure in models for Fanconi anemia (34) and ataxia telangiectasia (35).”
BackgroundAutofluorescence properties of murine embryonic stem cells during spontaneous differentiation phases
Santin, G., Paulis, M., Vezzoni, P., Pacchiana, G., Bottiroli, G. F., & Croce, A. C. (2013) · Lasers in Surgery and Medicine · doi:10.1002/lsm.22182 · Cited by 15
Absence of Wip1 partially rescues Atm deficiency phenotypes in mice
Darlington, Y. F., Nguyen, T.-A., Moon, S.-H., Herron, A., Rao, P., Zhu, C., Lu, X., & Donehower, L. A. (2011) · Oncogene · doi:10.1038/onc.2011.303 · Cited by 15
Physiological Functions of Mitochondrial Reactive Oxygen Species
Choi, T. G., & Kim, S. S. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.88386 · Cited by 22
“[97] Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I, et al.”
BackgroundXiao, Y., Wang, J., Song, H. K., Zou, P., Zhou, D., & Liu, L. (2012) · Leukemia Research · doi:10.1016/j.leukres.2012.11.006 · Cited by 16
“athological conditions in part via activation of p38 [6–9], we could ot detect significant increases in ROS production in both BMMCs and CD34+ cells from MDS patients.”
BackgroundHow close are we to targeting the leukemia stem cell?
Pei, S., & Jordan, C. T. (2012) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2012.10.003 · Cited by 15
“Several mutations, such as ATM and FOXO, impair self-renewal of hematopoietic stem cells via the induction of oxidative stress, which leads to “exhaustion” [13,14].”
BackgroundIdentification and characterization of mouse PSF1-binding protein, SLD5
Kong, L., Ueno, M., Itoh, M., Yoshioka, K., & Takakura, N. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.11.136 · Cited by 15
Zinkel, S. S., Yin, X., & Gross, A. (2012) · Oncogene · doi:10.1038/onc.2012.454 · Cited by 16
Ataxia Telangiectasia Mutated Dysregulation Results in Diabetic Retinopathy
Bhatwadekar, A. D., Duan, Y., Chakravarthy, H., Korah, M. M., Caballero, S., Busik, J. V., & Grant, M. B. (2015) · Stem Cells · doi:10.1002/stem.2235 · Cited by 15
“These findings are in agreement with a previous report [16] which showed a specific decrease in LTR-HSCs of ATM−/− chimeric mice.”
InfluentialRho GTPases in Hematopoietic Cells
van Hennik, P. B., & Hordijk, P. L. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.1440 · Cited by 15
“The ROS-dependent up-regulation of the p16 INK4-retinoblas-toma INK4-retinoblas-toma gene was found to cause the defects in reconstitution of hematopoiesis by the ATM (cid”
InfluentialSchuler, N., Timm, S., & Rübe, C. E. (2017) · Stem Cells · doi:10.1002/stem.2768 · Cited by 15
Identification and characterization of stem cell-specific transcription of PSF1 in spermatogenesis
Han, Y., Ueno, M., Nagahama, Y., & Takakura, N. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.01.133 · Cited by 15
Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome
Arai, H., Matsui, H., Chi, S., Utsu, Y., Masuda, S., Aotsuka, N., & Minami, Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25010652 · Cited by 14
“Intact ATM function has been well established as being critical for hematopoietic stem cell function [144], and ATM function and the associated signaling axis have been shown in vitro to modulate pathogenesis in AML [145,146].”
Background
Metadata
- Authors
- Ito, K., Hirao, A., Arai, F., Matsuoka, S., Takubo, K., Hamaguchi, I., Nomiyama, K., Hosokawa, K., Sakurada, K., Nakagata, N., Ikeda, Y., Mak, T. W., & Suda, T.
- Affiliations
- Keio University (JP)
- Kumamoto University (JP)
- University of Toronto (CA)
- Corresponding author
- Hirao, Atsushi
- Suda, Toshio
- ORCID
- Venue
- Nature
- Published
- 2004-10
- Volume
- 431
- Issue
- 7011
- Pages
- 997-1002
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2041897873
- Cited by
- 1,175
- References
- 30
- Citations by year
- 2026: 15 · 2025: 29 · 2024: 38 · 2023: 31 · 2022: 37 · 2021: 51 · 2020: 44 · 2019: 58 · 2018: 47 · 2017: 59 · 2016: 73 · 2015: 71 · 2014: 75 · 2013: 88 · 2012: 77
- FWCI
- 25.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- ATM, oxidative stress, hematopoietic stem cells, self-renewal, reactive oxygen species, ataxia telangiectasia, bone marrow failure, p16INK4a, retinoblastoma protein, DNA damage response, antioxidant therapy
- MeSH terms
- Acetylcysteine, Animals, Antioxidants, Cell Division, DNA-Binding Proteins, Hematopoiesis, Hematopoietic Stem Cells, Mice, Inbred C57BL, RNA, Messenger, Signal Transduction, Retinoblastoma Protein, Protein Serine-Threonine Kinases, Gene Deletion, Reactive Oxygen Species, Mice, Knockout, Oxidative Stress, Cell Cycle Proteins, Cell Lineage, Cyclin-Dependent Kinase Inhibitor p16, Tumor Suppressor Proteins, Mice, Ataxia Telangiectasia Mutated Proteins
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