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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]
Citations
Cites
Stem cells, cancer, and cancer stem cells
Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001) · Nature · doi:10.1038/35102167 · Cited by 9,738
A Single Ataxia Telangiectasia Gene with a Product Similar to PI-3 Kinase
Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., Tagle, D. A., Smith, S., Uziel, T., Sfez, S., et al. (1995) · Science · doi:10.1126/science.7792600 · Cited by 2,785
ATM and related protein kinases: safeguarding genome integrity
Shiloh, Y. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1011 · Cited by 2,577
Long-Term Lymphohematopoietic Reconstitution by a Single CD34-Low/Negative Hematopoietic Stem Cell
Osawa, M., Hanada, K., Hamada, H., & Nakauchi, H. (1996) · Science · doi:10.1126/science.273.5272.242 · Cited by 2,141
Tie2/Angiopoietin-1 Signaling Regulates Hematopoietic Stem Cell Quiescence in the Bone Marrow Niche
Arai, F., Hirao, A., Ohmura, M., Sato, H., Matsuoka, S., Takubo, K., Ito, K., Koh, G. Y., & Suda, T. (2004) · Cell · doi:10.1016/j.cell.2004.07.004 · Cited by 1,958
Self-citationBmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
Park, I.-K., Qian, D., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., Morrison, S. J., & Clarke, M. F. (2003) · Nature · doi:10.1038/nature01587 · Cited by 1,871
Jacobs, J. J. L., Kieboom, K., Marino, S., DePinho, R. A., & van Lohuizen, M. (1999) · Nature · doi:10.1038/16476 · Cited by 1,580
Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia
Barlow, C., Hirotsune, S., Paylor, R. E., Liyanage, M., Eckhaus, M., Collins, F. S., Shiloh, Y., Crawley, J. N., Ried, T., Tagle, D. A., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)80086-0 · Cited by 1,465
Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells.
Lessard, J., & Sauvageau, G. (2003) · Nature · doi:10.1038/nature01572 · Cited by 1,452
Hematopoietic Stem Cell Quiescence Maintained by p21 cip1/waf1
Cheng, T., Rodrigues, N., Shen, H., Yang, Y.-G., Dombkowski, D., Sykes, M., & Scadden, D. T. (2000) · Science · doi:10.1126/science.287.5459.1804 · Cited by 1,339
Cited by
Sorted by citations
Items 801–900 of 1,000
Sánchez-Ramírez, E., Ung, T. P. L., Stringari, C., & Aguilar‐Arnal, L. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04006-w · Cited by 15
“…the metabolic signature of NPCs correlates with their differentiation potential, showing that neuronal progenitors and glial progenitors have a different free/bound NADH ratio in line with evidence that energy metabolism and the redox state are important regulators of NSC [211, 212, 181, 213, 214].”
BackgroundMitonuclear Communication in Stem Cell Function
Peng, B., Wang, Y., & Zhang, H. (2024) · Cell Proliferation · doi:10.1111/cpr.13796 · Cited by 14
“For instance, in ATM-null mice, elevated ROS levels result in HSCs exhaustion via activation of the p38 MAPK pathway, a condition that can be ameliorated by long-term treatment with antioxidants or p38 MAPK inhibitors [336, 337].”
Telomere dysfunction and cell cycle checkpoints in hematopoietic stem cell aging
Ju, Z., Zhang, J., Gao, Y., & Cheng, T. (2011) · International Journal of Hematology · doi:10.1007/s12185-011-0882-z · Cited by 14
“24 weeks showed progressive bone marrow failure resulting from a defect in HSC function that was associated with elevated reactive oxygen species (ROS) [ 60 ].”
BackgroundTakaesu, G., Inagaki, M., Takubo, K., Mishina, Y. M., Hess, P. R., Dean, G. A., Yoshimura, A., Matsumoto, K., Suda, T., & Ninomiya‐Tsuji, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051073 · Cited by 14
“Bone marrow cells are constantly exposed to stressors such as reactive oxygen species [8] and cytokines such as TNF [37].”
BackgroundSelf-citationSMAR1 regulates free radical stress through modulation of AKR1a4 enzyme activity
Singh, S., Sreenath, K., Chavali, P. L., Roy, S., & Chattopadhyay, S. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.01.022 · Cited by 14
Genomic Stability in Stem Cells
Riz, I., & Hawley, R. G. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-227-8_6 · Cited by 14
“leagues [38] suggested that self-renewal capacity of HSCs”
BackgroundMitochondria and autophagy in adult stem cells: proliferate or differentiate
Lampert, M. A., & Gustafsson, Å. B. (2019) · Journal of Muscle Research and Cell Motility · doi:10.1007/s10974-019-09542-w · Cited by 14
ATM Paradoxically Promotes Oncogenic Transformation via Transcriptional Reprogramming
Liu, X., Hu, M., Liu, P., Jiao, M., Zhou, M., Lee, A. K., Li, F., & Li, C. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-2255 · Cited by 14
“The critical role of ATM for the induction of stemness in MPORCCtransformed cells was reminiscent of the requirement of ATM in the self-renewal of hematopoietic stem cells (42), lowered efficiency of iPSC formation from ATM-deficient fibroblasts (43, 44), and significantly attenuated ability to form teratoma in mice f…”
BackgroundThom, C. S., & Voight, B. F. (2020) · BMC Medical Genomics · doi:10.1186/s12920-020-00742-9 · Cited by 13
PIKK ing a way to regulate inflammation
Quek, H., Lim, Y. C., Lavin, M. F., & Roberts, T. L. (2017) · Immunology and Cell Biology · doi:10.1111/imcb.1001 · Cited by 15
“As Atm / mice age they undergo bone marrow failure due to the inability of stem cells to counteract reactive oxygen species induced stress, limiting self-renewal.(54) In summary, loss of ATM alters both innate and adaptive immune responses as well as leading to the”
BackgroundLeuzzi, V., D’Agnano, D., Menotta, M., Caputi, C., Chessa, L., & Magnani, M. (2018) · Neurology Genetics · doi:10.1212/nxg.0000000000000228 · Cited by 14
Differential response of normal and malignant urothelial cells to CHK1 and ATM inhibitors
Wang, W. T., Catto, J. W. F., & Meuth, M. (2014) · Oncogene · doi:10.1038/onc.2014.221 · Cited by 14
Yan, M., Zhu, C., Liu, N., Jiang, Y., Scofield, V. L., Riggs, P. K., Qiang, W., Lynn, W. S., & Wong, P. K. Y. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.05.008 · Cited by 14
“cells [26], and we have shown previously that NAC treatment delays the death of thymocytes taken from a human A-T patient [42].”
BackgroundInfluentialSieburg, H. B., Cattarossi, G., & Müller‐Sieburg, C. E. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003006 · Cited by 13
“Another proposal suggested that, in conjunction with oxidative stresses, high levels of reactive oxygen species (ROS) could be a damaging force acting on the long-term repopulating capacity of HSCs [18,19].”
BackgroundInfluentialBonora, M., Kahsay, A., & Pinton, P. (2021) · International review of cytology · doi:10.1016/bs.ircmb.2021.05.003 · Cited by 16
Zaker, F., Nasiri, N., Oodi, A., & Amirizadeh, N. (2013) · Hematology · doi:10.1179/1607845412y.0000000034 · Cited by 13
Paredes, R., Schneider, M., Stevens, A., White, D., Williamson, A., Muter, J., Pearson, S., Kelly, J. R., Connors, K., Wiseman, D., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky536 · Cited by 11
“As ATM-knockout leads to haematopoietic stem cell exhaustion (43), we surmised that the ATM-mediated phosphorylation event at S858/S860 would be linked to EVI1-mediated self-renewal.”
BackgroundTie, G., Yan, J., Khair, L., Tutto, A. A., & Messina, L. M. (2020) · Scientific Reports · doi:10.1038/s41598-020-60403-w · Cited by 14
Mitochondria and mtDNA integrity in stem cell function and differentiation
Hämäläinen, R. H. (2016) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2016.04.008 · Cited by 13
Recurrent germline variant in ATM associated with familial myeloproliferative neoplasms
Braunstein, E. M., Imada, E. L., Paşca, S., Wang, S., Chen, H., Alba, C., Hupalo, D. N., Wilkerson, M. D., Dalgard, C. L., Ghannam, J. Y., et al. (2022) · Leukemia · doi:10.1038/s41375-022-01797-6 · Cited by 12
Human melanocytes can be isolated, propagated and expanded from plucked anagen hair follicles
Dieckmann, C., Milkova, L., Hunziker, T., Emmendörffer, A., & Simon, J. C. (2010) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.01019.x · Cited by 12
Haploinsufficiency of SNEV Causes Defects of Hematopoietic Stem Cells Functions
Schraml, E., Voglauer, R., Fortschegger, K., Sibilia, M. C., Stelzer, I., Grillari, J., & Schauenstein, K. (2008) · Stem Cells and Development · doi:10.1089/scd.2007.0107 · Cited by 13
“This regenerative defect is dependent on increased formation of reactive oxygen species and the consequent accumulation of DNA damage [34].”
Gfer is a critical regulator of HSC proliferation
Sankar, U., & Means, A. R. (2011) · Cell Cycle · doi:10.4161/cc.10.14.15919 · Cited by 12
Mitsumori, T., Nozaki, Y., Kawashima, I., Yamamoto, T., Shobu, Y., Nakajima, K., Morishita, S., Komatsu, N., & Kirito, K. (2014) · Experimental Hematology · doi:10.1016/j.exphem.2014.05.007 · Cited by 12
Chang, Y.-H., Shaw, C., Wu, K., Hsieh, K.-H., Su, Y., & Lu, P. (2009) · Hemoglobin · doi:10.3109/03630260903212563 · Cited by 12
Chen, J., Gao, X., Yang, L., Fu, W., Liang, L., Li, J., Hu, B., Sun, Z.-J., Huang, S., Zhang, Y., et al. (2016) · Scientific Reports · doi:10.1038/srep26003 · Cited by 12
Wu, B., Yu, H., Wang, Y., Pan, Z., Zhang, Y., Li, T., Li, L., Zhang, W., Ge, L., Chen, Y., et al. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.05.025 · Cited by 12
Chen, S., Wang, J., Fang, Q., Gao, R., Shi, Q., Zhang, H., & Zhao, J. (2014) · Chinese Medical Journal · doi:10.3760/cma.j.issn.0366-6999.20133214 · Cited by 12
“HO-1 plays an important role in antioxidation and antiapoptosis, maintains the homeostasis, reduces the level of oxidative stress, and protects the cells.(29-31) We tried to put HO-1 into the bone marrow via the ability of mMSCs which can homing to HIM.”
BackgroundYoon, Y. M., Storm, K., Kamimae-Lanning, A. N., Goloviznina, N. A., & Kurre, P. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.09.005 · Cited by 15
“Error bars reflect SEM, and asterisks indicate *p % 0.05 and **p % 0.01. checkpoint (Burma et al., 2001; Ito et al., 2004), by intracellular flow cytometry.”
BackgroundInfluentialKeratinocyte stem cells are more resistant to UVA radiation than their direct progeny
Metral, É., Béchetoille, N., Demarne, F., Damour, O., & Rachidi, W. (2018) · PLoS ONE · doi:10.1371/journal.pone.0203863 · Cited by 12
Concerted roles of PTEN and ATM in controlling hematopoietic stem cell fitness and dormancy
Fortin, J., Bassi, C., Ramachandran, P., Li, W. Y., Tian, R., Zarrabi, I., Hill, G., Snow, B. E., Haight, J., Tobin, C., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci131698 · Cited by 13
“Indeed, studies in multiple mouse models have identified ROS elevation as a main cause of HSC dysfunction following disruption of regulators of the DNA damage response (15, 19, 38–40).”
BackgroundResultInfluentialSelf-citationHuiqin, C., Wei, W., Xu, R., & Cui, X. (2021) · Scientific Reports · doi:10.1038/s41598-021-91471-1 · Cited by 12
Fan, J., Cai, H., Li, Q., Du, Z., & Tan, W. (2012) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2012.01.017 · Cited by 12
Hematopoietic Stem Cells and Their Niche
Iwasaki, H., & Suda, T. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-347-3_2 · Cited by 12
“In Atm−/− mice, ROS elevation and defective HSCs’ self-renewal were observed (Ito et al. 2004) and, therefore, the activation of p38 MAPK was expected.”
BackgroundSelf-citationTharakan, S., Mascarenhas, J. O., & Tremblay, D. A. (2023) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2023.2277674 · Cited by 11
“ROS plays a role in hematopoietic stem cell (HSc) proliferation and migration through regulation of oncogenic tyrosine kinases including JAK2 [12]. it has been shown that ROS are increased in PMF and likely play a role in driving HScs out of quiescence [13,14].”
BackgroundWang, B., Wang, W., Xu, Y., Liu, R., Li, R., Yang, P., Zhao, C., Dai, Z., & Wang, Y. (2024) · Small · doi:10.1002/smll.202308539 · Cited by 11
Genetics of proliferative aging
Zucchero, T. M., & Ahmed, S. C. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.06.057 · Cited by 10
“Mice with mutations in genome stability genes such as ATM (Ito et al., 2004; Shiloh and Kastan, 2001), BRCA1 (Cao et al., 2003), XPA (de Boer et al., 2002) and RAD50 (Bender et al., 2002) display premature aging phenotypes for several proliferating tissues despite possessing long telomeres.”
InfluentialHe, T., Falwell, E., Brocca‐Cofano, E., & Pandrea, I. (2017) · Current Opinion in Virology · doi:10.1016/j.coviro.2017.07.012 · Cited by 12
Karabulutoglu, M., Finnon, R., Imaoka, T., Friedl, A. A., & Badie, C. (2018) · International Journal of Radiation Biology · doi:10.1080/09553002.2018.1490042 · Cited by 11
“For instance, in hypoxic states, transcription factors HIF-1a, FOXO3, and ATM downregulate intracellular ROS levels and maintain HSC pool in a BID, p16- and AKTdependent manner (Ito et al. 2004; Miyamoto et al. 2007; Suda et al. 2011; Maryanovich et al. 2012).”
BackgroundMitochondrial pyruvate metabolism and glutaminolysis toggle steady-state and emergency myelopoiesis
Pizzato, H. A., Wang, Y. A., Wolfgang, M. J., Finck, B. N., Patti, G. J., & Bhattacharya, D. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20221373 · Cited by 12
“…progenitors produce more reactive oxygen species than do upstream HSCs, and increasing levels of reactive oxygen species hinders HSC function (Inoue et al., 2010; Ito et al., 2004; Ito et al., 2006; Norddahl et al., 2011; Tan and Suda, 2018; Tothova et al., 2007; Wang et al., 2014).”
Gadd45a deletion aggravates hematopoietic stem cell dysfunction in ATM-deficient mice
Chen, Y., Yang, R., Guo, P., & Ju, Z. (2014) · Protein & Cell · doi:10.1007/s13238-013-0017-9 · Cited by 11
“As expected the ROS level of ATM−/− HSCs was higher than WT HSCs.”
InfluentialChoi, J. E., & Chung, W. (2018) · The Journal of Microbiology · doi:10.1007/s12275-019-8475-2 · Cited by 11
Autophagy and senescence: Insights from normal and cancer stem cells
Talukdar, S., Das, S. K., Emdad, L., & Fisher, P. B. (2021) · Advances in cancer research · doi:10.1016/bs.acr.2021.01.005 · Cited by 12
Lysosomes and Their Role in Regulating the Metabolism of Hematopoietic Stem Cells
Arif, T. (2022) · Biology · doi:10.3390/biology11101410 · Cited by 11
Oxidized low‐density lipoprotein induces hematopoietic stem cell senescence
Zhang, X., Zhang, G., Wang, Y., Liu, J., 魏强, Xu, C., Wang, J., & Wang, Y. (2013) · Cell Biology International · doi:10.1002/cbin.10121 · Cited by 11
The effects of proliferation and DNA damage on hematopoietic stem cell function determine aging
Khurana, S. (2016) · Developmental Dynamics · doi:10.1002/dvdy.24388 · Cited by 11
“Mice deficient in Atm expression (Atm) showed progressive BM failure after 24 weeks of age due to poorly functioning HSCs, while proliferation as well as differentiation of progenitors remained unaffected (Ito et al., 2004).”
BackgroundResultInfluentialZhao, B., Tan, T. L., Mei, Y., Yang, J. C., Yu, Y., Verma, A., Liang, Y., Gao, J., & Ji, P. (2016) · Scientific Reports · doi:10.1038/srep19589 · Cited by 13
“Furthermore, the upstream regulator of H2AX, ATM, which phosphorylates H2AX upon DNA damage, also plays an essential role in HSC self-renewal through the regulation of oxidative stress 36 .”
Stem cells bank on ATM machine
Whetton, A. D. (2004) · Nature Medicine · doi:10.1038/nm1104-1166 · Cited by 11
Uchiyama, T., Kawai, T., Nakabayashi, K., Nakazawa, Y., Goto, F., Okamura, K., Nishimura, T., Kato, K., Watanabe, N., Miura, A., et al. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.09.004 · Cited by 10
Halvarsson, C., Rörby, E., Eliasson, P., Lang, S., Soneji, S., & Jönsson, J. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2018.7551 · Cited by 10
“Excessive levels of ROS such as superoxide anion radicals ( O2 ), hydroxyl radicals ( OH), and hydrogen peroxide (H2O2) have been reported to limit the lifespan of stem cells (19, 20, 23).”
Yang, Z., & Jiang, H. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03522-x · Cited by 10
Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche
Vignon, C., Debeissat, C., Bourgeais, J., Gallay, N., Kouzi, F., Anginot, A., Picou, F., Guardiola, P., Ducrocq, E., Foucault, A., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228584 · Cited by 13
“Thus, the most primitive HSCs are reactive oxygen species (ROS)low, associated with a lesser activation of the p38 mitogen-activated protein kinase (MAPK) compared to their ROShigh more differentiated counterpart [13,14].”
BackgroundInfluentialp38α plays differential roles in hematopoietic stem cell activity dependent on aging contexts
Sorimachi, Y., Karigane, D., Ootomo, Y., Kobayashi, H., Morikawa, T., Otsu, K., Kubota, Y., Okamoto, S., Goda, N., & Takubo, K. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100563 · Cited by 11
“To evaluate whether conditional Atm-deficient (CAG-CreERT2) HSCs phenocopy the germ line Atmdeficient HSCs, we focused on DNA repair, as there are reports that germ line Atm loss impairs DNA repair in HSCs (2, 23), and analyzed DNA damage accumulation by counting phosphorylated H2A histone family member X (γH2AX) and…”
BackgroundInfluentialSelf-citationHSC-derived fatty acid oxidation in steady-state and stressed hematopoiesis
Mistry, J. J., Bowles, K. M., & Rushworth, S. A. (2022) · Experimental Hematology · doi:10.1016/j.exphem.2022.10.003 · Cited by 13
“The reduced reliance on mitochondrial function in the HSC allows for maintenance of low ROS levels, as HSCs are vulnerable to oxidative stress [31, 32].”
BackgroundClonal hematopoiesis and bone marrow inflammation
Xie, X., Su, M., Ren, K., Ma, X., Lv, Z., Li, Z., Mei, Y., & Ji, P. (2022) · Translational research · doi:10.1016/j.trsl.2022.11.004 · Cited by 10
Rettkowski, J., & Cabezas‐Wallscheid, N. (2025) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101323-023806 · Cited by 12
Hammad, M., Salma, R., Balosso, J., Rezvani, M., & Haghdoost, S. (2024) · Antioxidants · doi:10.3390/antiox13091035 · Cited by 9
“Therefore, we can conclude that using carbon ions or protons can affect the stemness”
Wei, Z., Lv, S., Wang, Y., Sun, M., Chi, G., Guo, J. X., Song, P., Fu, X., Zhang, S., & LI, Y. (2016) · Oncology Letters · doi:10.3892/ol.2016.4565 · Cited by 9
Jing, W., Zhang, L., Qin, F., Li, X., Guo, X., Li, Y., Qiu, C., & Zhao, Y. (2017) · Cellular Immunology · doi:10.1016/j.cellimm.2017.09.006 · Cited by 10
Talkhoncheh, M. S., Subramaniam, A., Magnusson, M., Kumar, P., Larsson, J., & Baudet, A. (2018) · Haematologica · doi:10.3324/haematol.2018.188466 · Cited by 9
“Additionally, NF-κB signaling has been linked to ROS production,(21) which must be tightly regulated to maintain HSPC function.(30) However, intracellular ROS levels were M.”
BackgroundChen, Y., Sun, J., Ju, Z., Wang, Z., & Li, T. (2021) · Cell Proliferation · doi:10.1111/cpr.12972 · Cited by 9
Oxidative Stress and X-ray Exposure Levels-Dependent Survival and Metabolic Changes in Murine HSPCs
Karabulutoglu, M., Finnon, R., Cruz-Garcia, L., Hill, M. A., & Badie, C. (2021) · Antioxidants · doi:10.3390/antiox11010011 · Cited by 9
Quiescence regulation by normal haematopoietic stem cells and leukaemia stem cells
Gudmundsson, K. O., & Du, Y. (2022) · FEBS Journal · doi:10.1111/febs.16472 · Cited by 10
Inhibition of ATM kinase rescues planarian regeneration after lethal radiation
Shiroor, D. A., Wang, K., Sanketi, B. D., Tapper, J. K., & Adler, C. E. (2023) · EMBO Reports · doi:10.15252/embr.202256112 · Cited by 8
“In other systems, ATM is required for cell cycle progression, stem cell renewal, apoptosis, and normal development even in the absence of severe DNA damage (Barlow et al , 1996; Herzog et al , 1998; Ito et al , 2004).”
Falanga, A., & Trinchero, A. (2013) · Haematologica · doi:10.3324/haematol.2013.085779 · Cited by 9
Pan, Y., Yuan, D., Zhang, J., Xu, P., Chen, H., & Shao, C. (2009) · Radiation Research · doi:10.1667/rr1491.1 · Cited by 9
Loss of ATM positively regulates Rac1 activity and cellular migration through oxidative stress
Tolbert, C. E., Beck, M. V., Kilmer, C. E., & Srougi, M. C. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.12.033 · Cited by 9
Molecular and Cellular Aspects of Macrophage Aging
Lloberas, J., Tur, J., Vico, T., & Celada, A. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_46 · Cited by 9
Regulation of the self-renewal ability of tissue stem cells by tumor-related genes
Naka, K., Ohmura, M., & Hirao, A. (2007) · Cancer Biomarkers · doi:10.3233/cbm-2007-34-504 · Cited by 9
“In an effort to manipulate intracellular ROS concentrations, Atm -deficient HSCs have been treated with the permeant thiol N -acetyl-l-cysteine (NAC), which acts as an anti-oxidative agent [19].”
Self-citationAltruistic Stem Cells and Cancer Stem Cells
Das, B. (2014) · doi:10.1002/9781118356203.ch7 · Cited by 9
Going through changes – the role of autophagy during reprogramming and differentiation
Petersen, M., Ebstrup, E. N., & Rodriguez, E. (2024) · Journal of Cell Science · doi:10.1242/jcs.261655 · Cited by 9
Complex Interactions in Regulation of Haematopoiesis—An Unexplored Iron Mine
De, R., Kulkarni, U. P., & Edison, E. S. (2021) · Genes · doi:10.3390/genes12081270 · Cited by 9
“Very high levels of ROS caused by several factors including iron overloading and chronic inflammation may also lead to HSC death by apoptosis [40].”
BackgroundZhao, K., Liu, J., Zhu, Y., Dong, X., Yin, R., Liu, X., Gao, H., Xiao, F., Gao, R., Wang, Q., et al. (2021) · Advanced Science · doi:10.1002/advs.202103838 · Cited by 7
Effects of different concentrations of nicotinamide on hematopoietic stem cells cultured in vitro
Ren, Y., Cui, Y., & Wang, H. (2024) · World Journal of Stem Cells · doi:10.4252/wjsc.v16.i2.163 · Cited by 8
Siow, K. M., Güngör, M., Wrona, D., Raimondi, F., Pastukhov, O., Tsapogas, P., Menzi, T., Schmitz, M., Kulcsár, P. I., Schwank, G., et al. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102229 · Cited by 8
“A balanced ROS level is crucial during hematopoiesis to support long-term repopulation ability of HSCs, 48,49 whereas oxidative stress caused by dysregulated ROS production can affect stem cell migration, development, proliferation, and repopulation potential.”
Zou, J., Zou, P., Lou, Y., Xiao, Y., Wang, J. X., & Liu, L. (2011) · Journal of Huazhong University of Science and Technology [Medical Sciences] · doi:10.1007/s11596-011-0566-1 · Cited by 8
Bai, L., Best, G., Xia, W., Peters, L., Wong, K., Wård, C., & Greenwood, M. J. (2018) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2018.06.014 · Cited by 8
Hassan, Q. N., Queen, N. J., & Cao, L. (2020) · Translational Cancer Research · doi:10.21037/tcr.2020.02.39 · Cited by 7
“Such changes are characterized by reduced cytotoxicity, impairment of antigen presenting cells (APCs), reduced antibody production, reduced self-renewal capacity, and altered inflammatory responses to insult (66-68).”
BackgroundMitochondria Transfer in Bone Marrow Hematopoietic Activity
Singh, A. K., & Cancelas, J. A. (2021) · Current Stem Cell Reports · doi:10.1007/s40778-020-00185-z · Cited by 8
Mohrin, M. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.01.034 · Cited by 9
Toward Elucidating Epigenetic and Metabolic Regulation of Stem Cell Lineage Plasticity in Skin Aging
Lyu, Y., & Ge, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.903904 · Cited by 9
Role of Caspase-10-P13tBID axis in erythropoiesis regulation
Lamarque, M., Gautier, E., Rodrigues, F., Guillem, F., Bayard, E., Broussard, C., Maciel, T. T., Arlet, J., Mayeux, P., Hermine, O., et al. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-01066-0 · Cited by 9
Targeting mitochondria to stimulate hematopoiesis
Girotra, M., Naveiras, O., & Vannini, N. (2020) · Aging · doi:10.18632/aging.102807 · Cited by 8
Saunders, R. A., Michniacki, T. F., Hames, C., Moale, H., Wilke, C. A., Kuo, M. E., Nguyen, J., Hartlerode, A. J., Moore, B. B., & Sekiguchi, J. (2021) · Scientific Reports · doi:10.1038/s41598-021-83531-3 · Cited by 7
Li, S., Yang, Y., Wen, J., He, M., Hu, Q., Zhang, K., & Weng, Q. (2023) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2023.115890 · Cited by 8
ATM in immunobiology: From lymphocyte development to cancer immunotherapy
Lee, J. (2025) · Translational Oncology · doi:10.1016/j.tranon.2024.102268 · Cited by 8
Targeting Poly(ADP)ribose polymerase in BCR/ABL1-positive cells
Hiroki, H., Ishii, Y., Piao, J., Namikawa, Y., Masutani, M., Honda, H., Akahane, K., Inukai, T., Morio, T., & Takagi, M. (2023) · Scientific Reports · doi:10.1038/s41598-023-33852-2 · Cited by 7
Research Progress on Cardiac Tissue Construction of Mesenchymal Stem Cells for Myocardial Infarction
Yang, G.-D., Ma, D., Ma, C., & Bai, Y. (2023) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x18666230823091017 · Cited by 7
Henry, E., Picou, F., Barroca, V., Déchamps, N., Sobrino, S., Six, E. M., Chenevier‐Gobeaux, C., Auberger, P., Hérault, O., Pflumio, F., et al. (2023) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szad049 · Cited by 8
“18-20 When CD34 + cells (and among them HSC) are cultured for gene therapy procedures, they can partially lose their functions mostly because ROS level increase by non-physiologic O 2 levels and growth factor signaling.”
Hyperbaric oxygen treatment effects on in vitro cultured umbilical cord blood CD34+ cells
Cheung, K. Y., Berry, A., Li, D., & Aljitawi, O. S. (2017) · Cytotherapy · doi:10.1016/j.jcyt.2017.08.020 · Cited by 7
Hasani, S., Boroujeni, M. E., Aliaghaei, A., Baghaei, K., & Rostami, A. (2018) · Cell Biology International · doi:10.1002/cbin.11056 · Cited by 5
A Bloody Feast—Nutritional Regulation of Hematopoiesis
Ussishkin, N., & Nachmani, D. (2023) · Experimental Hematology · doi:10.1016/j.exphem.2023.08.004 · Cited by 8
Tumor suppressive pathways in the control of neurogenesis
Bartesaghi, S., & Salomoni, P. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1063-9 · Cited by 8
“In this respect, HSCs appear to require low ROS to self-renew [232].”
BackgroundBid protects the mouse hematopoietic system following hydroxyurea-induced replicative stress
Liu, Y., Aiello, A., & Zinkel, S. S. (2012) · Cell Death and Differentiation · doi:10.1038/cdd.2012.38 · Cited by 7
“Atm / mice demonstrate progressive bone marrow failure due to a depletion of LSK cells, as well as HSC function.(15)”
BackgroundUrata, Y., Goto, S., Luo, L., Doi, H., Kitajima, Y., Masuda, S., Ono, Y., & Li, T. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.10.090 · Cited by 7
Sustained p16INK4a expression is required to prevent IR-induced tumorigenesis in mice
Palacio, L., Krishnan, V., Le, N. L. O., Sharpless, N. E., & Beausejour, C. M. (2016) · Oncogene · doi:10.1038/onc.2016.298 · Cited by 7
“Alternatively, p16 INK4a expression may rise in response to the accumulation of reactive oxygen species or as a bystander effect of IR-induced loss of tissue homeostasis 10, 11, 32 .”
Lee, J., Kim, O., Lee, S. C., Kim, K., Shin, J. S., Hong, H., Choi, H. J., & Kim, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225589 · Cited by 9
Defining the General Principles of Stem Cell Aging: Lessons from Organismal Models
Koyuncu, S., Irmak, D., Sáez, I., & Vílchez, D. (2015) · Current Stem Cell Reports · doi:10.1007/s40778-015-0017-1 · Cited by 8
ATM is required for SOD2 expression and homeostasis within the mammary gland
Dyer, L. M., Kepple, J. D., Ai, L., Kim, W.-J., Stanton, V. L., Reinhard, M. K., Backman, L. R. F., Streitfeld, W. S., Babu, N. R., Treiber, N., et al. (2017) · Breast Cancer Research and Treatment · doi:10.1007/s10549-017-4424-0 · Cited by 7
“This finding is consistent with previous studies from the Paull lab indicating that ATM is catalytically acti- vated in response to reactive oxygen species (ROS) [14].”
InfluentialThe fanconi anemia pathway promotes homologous recombination repair in DT40 cell line
Takata, M., Yamamoto, K., Matsushita, N., Kitao, H., Hirano, S., & Ishaiai, M. (2006) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-1-4020-4896-8_17 · Cited by 7
“Recent studies indicate genes involved in DNA damage response are required for maintenance of bone marrow stem cells (O’Driscoll et al., 2001; Bender et al., 2002; Ito et al., 2004), possibly protecting against oxidative damage (Ito et al.”
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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