TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species
Open accessAbstract
The tuberous sclerosis complex (TSC)-mammalian target of rapamycin (mTOR) pathway is a key regulator of cellular metabolism. We used conditional deletion of Tsc1 to address how quiescence is associated with the function of hematopoietic stem cells (HSCs). We demonstrate that Tsc1 deletion in the HSCs drives them from quiescence into rapid cycling, with increased mitochondrial biogenesis and elevated levels of reactive oxygen species (ROS). Importantly, this deletion dramatically reduced both hematopoiesis and self-renewal of HSCs, as revealed by serial and competitive bone marrow transplantation. In vivo treatment with an ROS antagonist restored HSC numbers and functions. These data demonstrated that the TSC-mTOR pathway maintains the quiescence and function of HSCs by repressing ROS production. The detrimental effect of up-regulated ROS in metabolically active HSCs may explain the well-documented association between quiescence and the "stemness" of HSCs.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Signaling through the PTEN-AKT-mTOR pathway upstream of FoxO senses and controls ROS and regulates HSC self-renewal and survival.
“A decline in long-term regeneration capacity of HSCs in mice with conditional deletion of phosphatase and tensin homolog (PTEN) and double deficiency of protein kinase B (AKT) 1 and 2 also indicates that signaling through the PTEN–AKT–mammalian target of rapamycin (mTOR) pathway, upstream of FoxO, senses and controls ROS and regulates HSC self-renewal and survival19–21.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [20]
mTOR is a key controller of ROS levels and autophagy in HSCs.
“For example, the mTOR pathway has been shown to be a major regulator of both ROS levels and autophagy in HSCs20,78,80, (Fig. 3).”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [20]
Increased mTOR activity can cause certain cells to undergo differentiation or senescence, thereby exiting the proliferative cell pool.
“increased mTOR activity can also cause certain cells to undergo differentiation or senescence, thereby exiting the proliferative cell pool (Castilho et al., 2009; Chen et al., 2008; Lee et al., 2010; Liu et al., 2007; Zhang et al., 2006; reviewed in Iglesias-Bartolome and Gutkind, 2011).”
From mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis (2012) · cites this paper as Chen et al., 2008
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787 · see citing works
Kiel, M. J., Yilmaz, Ö. H., Iwashita, T., Yilmaz, O. H., Terhorst, C., & Morrison, S. J. (2005) · Cell · doi:10.1016/j.cell.2005.05.026 · Cited by 3,168 · see citing works
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083 · see citing works
Self-citationIdentification of the haematopoietic stem cell niche and control of the niche size
Zhang, J., Niu, C. S., Ye, L., Huang, H., He, X. C., Tong, W.-G., Ross, J., Haug, J., Johnson, T. J., Feng, J. Q., et al. (2003) · Nature · doi:10.1038/nature02041 · Cited by 2,948 · see citing works
The relationship between the spleen colony-forming cell and the haemopoietic stem cell.
Schofield, R. (1978) · PubMed · Cited by 2,319 · see citing works
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 · see citing works
Inducible Gene Targeting in Mice
Kühn, R., Schwenk, F., Aguet, M., & Rajewsky, K. (1995) · Science · doi:10.1126/science.7660125 · Cited by 1,915 · see citing works
Hypoxia signalling in cancer and approaches to enforce tumour regression
Pouysségur, J., Dayan, F., & Mazure, N. M. (2006) · Nature · doi:10.1038/nature04871 · Cited by 1,676 · see citing works
Identification of the Tuberous Sclerosis Gene <i>TSC1</i> on Chromosome 9q34
Slegtenhorst, M. V., Hoogt, R. D., Hermans, C., Nellist, M., Janssen, B., Verhoef, S., Lindhout, D., Ouweland, A. V. D., Halley, D., Young, J., et al. (1997) · Science · doi:10.1126/science.277.5327.805 · Cited by 1,648 · see citing works
Identification and characterization of the tuberous sclerosis gene on chromosome 16
(1993) · Cell · doi:10.1016/0092-8674(93)90618-z · Cited by 1,645 · see citing works
FoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress
Tothova, Z., Kollipara, R., Huntly, B. J., Lee, B. H., Castrillon, D. H., Cullen, D. E., McDowell, E. P., Lazo-Kallanian, S., Williams, I. R., Sears, C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.01.003 · Cited by 1,562 · see citing works
Growing roles for the mTOR pathway
Sarbassov, D. D., Ali, S. M., & Sabatini, D. M. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.09.009 · Cited by 1,556 · see citing works
mTOR controls mitochondrial oxidative function through a YY1–PGC-1α transcriptional complex
Cunningham, J. T., Rodgers, J. T., Arlow, D. H., Vazquez, F., Mootha, V. K., & Puigserver, P. (2007) · Nature · doi:10.1038/nature06322 · Cited by 1,488 · see citing works
Spradling, A. C., Drummond‐Barbosa, D., & Kai, T. (2001) · Nature · doi:10.1038/35102160 · Cited by 1,429 · see citing works
Differentiation and proliferation of hematopoietic stem cells
Ogawa, M. (1993) · Blood · doi:10.1182/blood.v81.11.2844.2844 · Cited by 1,395 · see citing works
Brugarolas, J., Lei, K., Hurley, R. L., Manning, B. D., Reiling, J. H., Hafen, E., Witters, L. A., Ellisen, L. W., & Kaelin, W. G. (2004) · Genes & Development · doi:10.1101/gad.1256804 · Cited by 1,384 · see citing works
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 · see citing works
Bone-marrow haematopoietic-stem-cell niches
Wilson, A., & Trumpp, A. (2006) · Nature reviews. Immunology · doi:10.1038/nri1779 · Cited by 1,350 · see citing works
Hematopoietic Stem Cell Quiescence Maintained by p21 <sup>cip1/waf1</sup>
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 · see citing works
Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells
Yilmaz, Ö. H., Valdez, R., Theisen, B. K., Guo, W., Ferguson, D. O., Wu, H., & Morrison, S. J. (2006) · Nature · doi:10.1038/nature04703 · Cited by 1,272 · see citing works
Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis
Cully, M., You, H., Levine, A. J., & Mak, T. W. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1819 · Cited by 1,233 · see citing works
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 · see citing works
Essential role for nuclear PTEN in maintaining chromosomal integrity
Shen, W. H., Balajee, A. S., Wang, J., Wu, H., Eng, C., Pandolfi, P. P., & Yin, Y. (2007) · Cell · doi:10.1016/j.cell.2006.11.042 · Cited by 979 · see citing works
Dysregulation of the TSC-mTOR pathway in human disease
Inoki, K., Corradetti, M. N., & Guan, K. (2004) · Nature Genetics · doi:10.1038/ng1494 · Cited by 970 · see citing works
Self-citationThe role of oxygen availability in embryonic development and stem cell function
Simon, M. C., & Keith, B. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2354 · Cited by 966 · see citing works
Akt regulates growth by directly phosphorylating Tsc2
Potter, C. J., Pedraza, L. G., & Xu, T. (2002) · Nature Cell Biology · doi:10.1038/ncb840 · Cited by 959 · see citing works
Jang, Y.-Y., & Sharkis, S. J. (2007) · Blood · doi:10.1182/blood-2007-05-087759 · Cited by 894 · see citing works
Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia
Parmar, K., Mauch, P., Vergilio, J.-A., Sackstein, R., & Down, J. D. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701152104 · Cited by 867 · see citing works
PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention
Zhang, J., Grindley, J. C., Yin, T., Jayasinghe, S., He, X. C., Ross, J. T., Haug, J. S., Rupp, D., Porter-Westpfahl, K. S., Wiedemann, L. M., et al. (2006) · Nature · doi:10.1038/nature04747 · Cited by 817 · see citing works
Yoshihara, H., Arai, F., Hosokawa, K., Hagiwara, T., Takubo, K., Nakamura, Y., Gomei, Y., Iwasaki, H., Matsuoka, S., Miyamoto, K., et al. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.10.020 · Cited by 816 · see citing works
Ubiquitination regulates PTEN nuclear import and tumor suppression
Trotman, L. C., Wang, X., Alimonti, A., Chen, Z., Teruya-Feldstein, J., Yang, H., Pavletich, N. P., Carver, B. S., Cordon-Cardo, C., Erdjument-Bromage, H., et al. (2007) · Cell · doi:10.1016/j.cell.2006.11.040 · Cited by 748 · see citing works
Nilsson, S. K., Johnston, H. M., & Coverdale, J. (2001) · Blood · doi:10.1182/blood.v97.8.2293 · Cited by 575 · see citing works
Lajtha, L. G. (1979) · Differentiation · doi:10.1111/j.1432-0436.1979.tb01007.x · Cited by 558 · see citing works
Potter, C. J., Huang, H., & Xu, T. (2001) · Cell · doi:10.1016/s0092-8674(01)00333-6 · Cited by 522 · see citing works
Fleming, H. E., Janzen, V., Celso, C. L., Guo, J., Leahy, K. M., Kronenberg, H. M., & Scadden, D. T. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.01.003 · Cited by 500 · see citing works
The expanding TOR signaling network
Martin, D. E., & Hall, M. N. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.02.008 · Cited by 496 · see citing works
TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth.Preprint
Gao, X., & Pan, D. (2001) · Genes & Development · doi:10.1101/gad.901101 · Cited by 484 · see citing works
Pendergrass, W., Wolf, N. S., & Poot, M. J. M. (2004) · Cytometry Part A · doi:10.1002/cyto.a.20033 · Cited by 476 · see citing works
Regulation of mTOR and Cell Growth in Response to Energy Stress by REDD1
Sofer, A., Lei, K., Johannessen, C. M., & Ellisen, L. W. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.14.5834-5845.2005 · Cited by 449 · see citing works
Bowie, M. B., McKnight, K. D., Kent, D. G., McCaffrey, L., Hoodless, P. A., & Eaves, C. J. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28310 · Cited by 380 · see citing works
The role of hypoxia in the maintenance of hematopoietic stem cells
Cipolleschi, M., Sbarba, P. D., & Olivotto, M. (1993) · Blood · doi:10.1182/blood.v82.7.2031.2031 · Cited by 373 · see citing works
Uhlmann, E. J., Wong, M., Baldwin, R. L., Bajenaru, M. L., Onda, H., Kwiatkowski, D. J., Yamada, K., & Gutmann, D. H. (2002) · Annals of Neurology · doi:10.1002/ana.10283 · Cited by 372 · see citing works
Mikkola, H. K. A., Klintman, J., Yang, H., Hock, H., Schlaeger, T. M., Fujiwara, Y., & Orkin, S. H. (2003) · Nature · doi:10.1038/nature01345 · Cited by 371 · see citing works
Chow, D. C., Wenning, L. A., Miller, W. M., & Papoutsakis, E. T. (2001) · Biophysical Journal · doi:10.1016/s0006-3495(01)75733-5 · Cited by 317 · see citing works
Reiling, J. H., & Hafen, E. (2004) · Genes & Development · doi:10.1101/gad.322704 · Cited by 291 · see citing works
Complexity of the TOR signaling network
Inoki, K., & Guan, K. (2006) · Trends in Cell Biology · doi:10.1016/j.tcb.2006.02.002 · Cited by 191 · see citing works
Self-citationON THE CONCEPT OF THE CELL CYCLE.
Lajtha, L. G. (1963) · PubMed · Cited by 159 · see citing works
Growth Control Under Stress: mTOR Regulation through the REDD1-TSC Pathway
Ellisen, L. W. (2005) · Cell Cycle · doi:10.4161/cc.4.11.2139 · Cited by 131 · see citing works
Ivanović, Z., Bartolozzi, Bernabei, Cipolleschi, Rovida, E., Milenković, Praloran, & Sbarba (2000) · British Journal of Haematology · doi:10.1046/j.1365-2141.2000.01842.x · Cited by 106 · see citing works
Hypoxia-reoxygenation induces premature senescence in FA bone marrow hematopoietic cells
Zhang, X., Li, J., Sejas, D. P., & Pang, Q. (2005) · Blood · doi:10.1182/blood-2004-08-3033 · Cited by 59 · see citing works
Suzuki, T., Das, S. K., Inoue, H., Kazami, M., Hino, O., Kobayashi, T., Yeung, R. S. W., Kobayashi, K., Tadokoro, T., & Yamamoto, Y. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.01.077 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
ROS function in redox signaling and oxidative stress
Schieber, M., & Chandel, N. S. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.034 · Cited by 6,931 · see citing works
Regulation and function of mTOR signalling in T cell fate decisions
Chi, H. (2012) · Nature Reviews Immunology · doi:10.1038/nri3198 · Cited by 1,035 · see citing works
Metabolic Regulation of Hematopoietic Stem Cells in the Hypoxic Niche
Suda, T., Takubo, K., & Semenza, G. L. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2011.09.010 · Cited by 844 · see citing works
Stem cell aging: mechanisms, regulators and therapeutic opportunities
Oh, J., Lee, Y. D., & Wagers, A. J. (2014) · Nature Medicine · doi:10.1038/nm.3651 · Cited by 796 · see citing works
Le Belle, J. E., Orozco, N. M., Paucar, A. A., Saxe, J. P., Mottahedeh, J., Pyle, A. D., Wu, H., & Kornblum, H. I. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2010.11.028 · Cited by 789 · see citing works
Mitochondria are required for pro-ageing features of the senescent phenotype
Correia‐Melo, C., Marques, F. D., Anderson, R., Hewitt, G., Hewitt, R., Cole, J., Carroll, B. M., Miwa, S., Birch, J., Merz, A., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201592862 · Cited by 796 · see citing works
mTORC1 controls the adaptive transition of quiescent stem cells from G0 to GAlert
Rodgers, J. T., King, K. Y., Brett, J. O., Cromie, M. J., Charville, G. W., Maguire, K. K., Brunson, C., Mastey, N., Liu, L., Tsai, C.-R., et al. (2014) · Nature · doi:10.1038/nature13255 · Cited by 776 · see citing works
mTOR Regulation and Therapeutic Rejuvenation of Aging Hematopoietic Stem Cells
Chen, C., Liu, Y., Liu, Y., & Zheng, P. (2009) · Science Signaling · doi:10.1126/scisignal.2000559 · Cited by 680 · see citing works
Self-citationThe autophagy protein Atg7 is essential for hematopoietic stem cell maintenance
Mortensen, M., Soilleux, E. J., Djordjevic, G., Tripp, R., Lutteropp, M., Sadighi-Akha, E., Stranks, A. J., Glanville, J., Knight, S., W. Jacobsen, S.-E., et al. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20101145 · Cited by 657 · see citing works
Notch Signaling Is Necessary to Maintain Quiescence in Adult Muscle Stem Cells
Bjornson, C. R. R., Cheung, T. H., Liu, L., Tripathi, P. V., Steeper, K. M., & Rando, T. A. (2012) · Stem Cells · doi:10.1002/stem.773 · Cited by 598 · see citing works
Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies
Lee, J. H., Budanov, A. V., Park, E. J., Birse, R., Kim, T. E., Perkins, G. A., Ocorr, K., Ellisman, M. H., Bodmer, R., Bier, E., et al. (2010) · Science · doi:10.1126/science.1182228 · Cited by 570 · see citing works
Metabolic switching and fuel choice during T‐cell differentiation and memory development
van der Windt, G. J. W., & Pearce, E. L. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01150.x · Cited by 563 · see citing works
Rapalogs and mTOR inhibitors as anti-aging therapeutics
Lamming, D. W., Ye, L., Sabatini, D. M., & Baur, J. A. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64099 · Cited by 531 · see citing works
Metabolic regulation of stem cell function in tissue homeostasis and organismal ageing
Chandel, N. S., Jasper, H., Ho, T. T., & Passegué, E. (2016) · Nature Cell Biology · doi:10.1038/ncb3385 · Cited by 326 · see citing works
Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation
Tang, A. H., & Rando, T. A. (2014) · The EMBO Journal · doi:10.15252/embj.201488278 · Cited by 294 · see citing works
AKT1 and AKT2 maintain hematopoietic stem cell function by regulating reactive oxygen species
Juntilla, M. M., Patil, V. D., Calamito, M., Joshi, R. P., Birnbaum, M. J., & Koretzky, G. A. (2010) · Blood · doi:10.1182/blood-2009-09-241000 · Cited by 284 · see citing works
Iglesias-Bartolome, R., Patel, V., Cotrim, A., Leelahavanichkul, K., Molinolo, A. A., Mitchell, J. B., & Gutkind, J. S. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.06.007 · Cited by 284 · see citing works
Changes in Regenerative Capacity through Lifespan
Yun, M. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161025392 · Cited by 216 · see citing works
The cell fate: senescence or quiescence
Terzi, M. Y., Izmirli, M., & Gogebakan, B. (2016) · Molecular Biology Reports · doi:10.1007/s11033-016-4065-0 · Cited by 208 · see citing works
Cell cycle arrest is not senescence
Blagosklonny, M. V. (2011) · Aging · doi:10.18632/aging.100281 · Cited by 217 · see citing works
Pala, F., Di Girolamo, D., Mella, S., Yennek, S., Chatre, L., Ricchetti, M., & Tajbakhsh, S. (2018) · Journal of Cell Science · doi:10.1242/jcs.212977 · Cited by 184 · see citing works
Oxidative Stress Regulation of Stem and Progenitor Cells
Pervaiz, S., Taneja, R., & Ghaffari, S. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2804 · Cited by 176 · see citing works
Shao, L., Feng, W., Li, H., Gardner, D., Luo, Y., Wang, Y., Liu, L., Meng, A., Sharpless, N. E., & Zhou, D. (2014) · Blood · doi:10.1182/blood-2013-07-515619 · Cited by 165 · see citing works
Nutrient-sensing pathways and metabolic regulation in stem cells
Ochocki, J. D., & Simon, M. C. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201303110 · Cited by 140 · see citing works
Stem Cells, Redox Signaling, and Stem Cell Aging
Liang, R., & Ghaffari, S. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5300 · Cited by 106 · see citing works
Neuroprotective effects of dietary restriction: Evidence and mechanisms
Pani, G. (2015) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2015.03.004 · Cited by 103 · see citing works
mTOR-Dependent Cell Proliferation in the Brain
Ryskalin, L., Lazzeri, G., Flaibani, M., Biagioni, F., Gambardella, S., Frati, A., & Fornai, F. (2017) · BioMed Research International · doi:10.1155/2017/7082696 · Cited by 86 · see citing works
Metabolic regulation of somatic stem cells in vivo
Meacham, C. E., DeVilbiss, A. W., & Morrison, S. J. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00462-1 · Cited by 85 · see citing works
Rapamycin improves healthspan but not inflammaging in <i>nfκb1</i><sup>−/−</sup> mice
Correia‐Melo, C., Birch, J., Fielder, E., Rahmatika, D., Taylor, J., Chapman, J., Lagnado, A., Carroll, B. M., Miwa, S., Richardson, G., et al. (2019) · Aging Cell · doi:10.1111/acel.12882 · Cited by 77 · see citing works
“Fur- thermore, mTOR has been shown to negatively impact on stem cell function potentially via mitochondrial dysfunction and ROS generation (Chen et al., 2008; Sousa‐Victor et al., 2014).”
BackgroundNK cell development requires Tsc1-dependent negative regulation of IL-15-triggered mTORC1 activation
Yang, M., Chen, S., Du, J., He, J., Wang, Y., Li, Z., Liu, G., Peng, W., Zeng, X., Li, D., et al. (2016) · Nature Communications · doi:10.1038/ncomms12730 · Cited by 73 · see citing works
Wang, Y., Liu, Y., Tang, F., Bernot, K. M., Schore, R., Marcucci, G., Caligiuri, M. A., Zheng, P., & Liu, Y. (2014) · Blood · doi:10.1182/blood-2013-12-544221 · Cited by 69 · see citing works
Self-citationSuo, M., Rommelfanger, M. K., Chen, Y., Amro, E. M., Han, B., Chen, Z., Szafranski, K., Chakkarappan, S. R., Boehm, B. O., MacLean, A. L., et al. (2022) · Blood · doi:10.1182/blood.2021012197 · Cited by 57 · see citing works
The role of mitochondria in <scp>mTOR</scp>‐regulated longevity
Wei, Y., Zhang, Y., Cai, Y., & Xu, M. (2015) · Biological Reviews · doi:10.1111/brv.12103 · Cited by 56 · see citing works
The response to DNA damage during differentiation: Pathways and consequences
Fortini, P., Ferretti, C., & Dogliotti, E. (2013) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2013.03.004 · Cited by 45 · see citing works
- Authors
- Chen, C., Liu, Y., Liu, R., Ikenoue, T., Guan, K.-L., Liu, Y., & Zheng, P.
- Affiliations
- 1Program of Cell and Developmental Biology
- 2Division of Immunotherapy, Department of Surgery
- University of Michigan (US)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2008-09-22
- Volume
- 205
- Issue
- 10
- Pages
- 2397-2408
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2556783
- OpenAlex
- W2130202974
- Cited by
- 682
- References
- 51
- Citations by year
- 2026: 18 · 2025: 16 · 2024: 25 · 2023: 25 · 2022: 36 · 2021: 44 · 2020: 37 · 2019: 44 · 2018: 47 · 2017: 37 · 2016: 48 · 2015: 42 · 2014: 57 · 2013: 62 · 2012: 40
- FWCI
- 22.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- American Cancer Society
- University of Michigan
- National Institutes of Health
- University of Michigan Comprehensive Cancer Center
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- tuberous sclerosis complex, mTOR signaling, hematopoietic stem cells, stem cell quiescence, mitochondrial biogenesis, reactive oxygen species, hematopoiesis, self-renewal, stemness, bone marrow transplantation, cellular metabolism
- MeSH terms
- Tuberous Sclerosis Complex 1 Protein, Animals, Hematopoiesis, Hematopoietic Stem Cells, Immunosuppressive Agents, Mice, Inbred C57BL, Mitochondria, Mutation, Protein Kinases, Bone Marrow Transplantation, Reactive Oxygen Species, Mice, Knockout, Sirolimus, Tumor Suppressor Proteins, Cell Proliferation, Mice, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
