Hematopoietic Stem Cell Quiescence Maintained by p21 cip1/waf1
Abstract
Relative quiescence is a defining characteristic of hematopoietic stem cells, while their progeny have dramatic proliferative ability and inexorably move toward terminal differentiation. The quiescence of stem cells has been conjectured to be of critical biologic importance in protecting the stem cell compartment, which we directly assessed using mice engineered to be deficient in the G 1 checkpoint regulator, cyclin-dependent kinase inhibitor, p21 cip1/waf1 (p21). In the absence of p21, hematopoietic stem cell proliferation and absolute number were increased under normal homeostatic conditions. Exposing the animals to cell cycle–specific myelotoxic injury resulted in premature death due to hematopoietic cell depletion. Further, self-renewal of primitive cells was impaired in serially transplanted bone marrow from p21 −/− mice, leading to hematopoietic failure. Therefore, p21 is the molecular switch governing the entry of stem cells into the cell cycle, and in its absence, increased cell cycling leads to stem cell exhaustion. Under conditions of stress, restricted cell cycling is crucial to prevent premature stem cell depletion and hematopoietic death.
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Reduced quiescent stem cells in p21-deficient cells correlates with impaired self-renewal and eventual stem cell pool exhaustion.
“The reduced number of quiescent stem cells correlates with impaired self-renewal capacity of p21-deficient cells, which ultimately results in an exhaustion of the stem cell pool65,72.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [65]
A proper quiescence-proliferation balance is needed to keep the stem cell pool available for repeated tissue regeneration, as shown in Drosophila intestine, HSCs and p21-null neural stem cells.
“Maintaining this balance is crucial to sustain the stem cell pool through multiple rounds of tissue regeneration, as demonstrated by studies in the Drosophila intestine, and in HSCs and neural stem cells of p21-null mice109,130,131.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [130]
When cell cycle control is lost, too much proliferation speeds up depletion of these stem cell pools.
“Excessive proliferation caused by loss of cell cycle regulation results in accelerated exhaustion of these stem cell pools.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [130]
Stem cell exhaustion may be driven by an imbalance between quiescence and proliferation.
“Stem cell exhaustion may also be driven by an imbalance of stem cell quiescence and proliferation.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [130]
Cites
Joyce, A. (1989) · Nursing Children and Young People · doi:10.7748/paed.1.6.21.s21 · Cited by 3,410 · see citing works
Inhibitors of mammalian G1 cyclin-dependent kinases.Preprint
Sherr, C. J., & Roberts, J. M. (1995) · Genes & Development · doi:10.1101/gad.9.10.1149 · Cited by 3,222 · see citing works
G1 phase progression: Cycling on cue
Sherr, C. J. (1994) · Cell · doi:10.1016/0092-8674(94)90540-1 · Cited by 2,675 · see citing works
Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
Deng, C., Zhang, P., Wade Harper, J., Elledge, S. J., & Leder, P. (1995) · Cell · doi:10.1016/0092-8674(95)90039-x · Cited by 2,113 · see citing works
New functional activities for the p21 family of CDK inhibitors.
LaBaer, J., Garrett, M. D., Stevenson, L. F., Slingerland, J. M., Sandhu, C., Chou, H. S., Fattaey, A., & Harlow, E. (1997) · Genes & Development · doi:10.1101/gad.11.7.847 · Cited by 1,402 · 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
Radiation-induced cell cycle arrest compromised by p21 deficiency
Brugarolas, J., Chandrasekaran, C., Gordon, J. I., Beach, D., Jacks, T., & Hannon, G. J. (1995) · Nature · doi:10.1038/377552a0 · Cited by 1,242 · see citing works
Holyoake, T. L., Jiang, X., Eaves, C. J., & Eaves, A. C. (1999) · Blood · doi:10.1182/blood.v94.6.2056 · Cited by 511 · see citing works
Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy.
Mauch, P., Constine, L., Greenberger, J., Knospe, W., Sullivan, J., Liesveld, J. L., & Deeg, H. J. (1995) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(94)00430-s · Cited by 507 · see citing works
Telomeres in the mouse have large inter-chromosomal variations in the number of T 2 AG 3 repeats
Zijlmans, J. M. J. M., Martens, U. M., Poon, S. S. S., Raap, A. K., Tanke, H. J., Ward, R. K., & Lansdorp, P. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7423 · Cited by 501 · see citing works
Resistance to Apoptosis Conferred by Cdk Inhibitors During Myocyte Differentiation
Wang, J., & Walsh, K. (1996) · Science · doi:10.1126/science.273.5273.359 · Cited by 490 · see citing works
An in vitro limiting-dilution assay of long-term repopulating hematopoietic stem cells in the mouse
Ploemacher, R., van der Sluijs, J., Voerman, J., & Brons, N. (1989) · Blood · doi:10.1182/blood.v74.8.2755.2755 · Cited by 396 · see citing works
Functional Isolation and Characterization of Human Hematopoietic Stem Cells
Berardi, A. C., Wang, A., Levine, J. D., Lopez, P., & Scadden, D. T. (1995) · Science · doi:10.1126/science.7528940 · Cited by 371 · see citing works
Self-citationCompetitive repopulation: a new assay for long-term stem cell functional capacity
Harrison, D. (1980) · Blood · doi:10.1182/blood.v55.1.77.77 · Cited by 329 · see citing works
Harrison, D. E., & Astle, C. M. (1982) · The Journal of Experimental Medicine · doi:10.1084/jem.156.6.1767 · Cited by 281 · see citing works
Cunto, F. D., Topley, G., Calautti, E., Hsiao, J., Ong, L., Seth, P. K., & Dotto, G. P. (1998) · Science · doi:10.1126/science.280.5366.1069 · Cited by 275 · see citing works
Ploemacher, R., der Sluijs, J. V., van Beurden, C., Baert, M., & Chan, P. (1991) · Blood · doi:10.1182/blood.v78.10.2527.2527 · Cited by 261 · see citing works
Wolf, N. S., Koné, A., Priestley, G. V., & Bartelmez, S. (1993) · PubMed · Cited by 257 · see citing works
5-Fluorouracil spares hemopoietic stem cells responsible for long-term repopulation.
Lerner, C. P., & Harrison, D. E. (1990) · PubMed · Cited by 246 · see citing works
Harrison, D. E., Astle, C. M., & Delaittre, J. A. (1978) · The Journal of Experimental Medicine · doi:10.1084/jem.147.5.1526 · Cited by 228 · see citing works
Gothot, A., Pyatt, R. E., McMahel, J., Rice, S. E., & Srour, E. F. (1997) · Blood · doi:10.1182/blood.v90.11.4384 · Cited by 191 · see citing works
Uchida, N., Aguila, H. L., Fleming, W., Jerabek, L., & Weissman, I. L. (1994) · Blood · doi:10.1182/blood.v83.12.3758.bloodjournal83123758 · Cited by 181 · see citing works
Effects of transplantation on the primitive immunohematopoietic stem cell.
Harrison, D. E., Stone, M., & Astle, C. M. (1990) · The Journal of Experimental Medicine · doi:10.1084/jem.172.2.431 · Cited by 131 · see citing works
ES cells have only a limited lymphopoietic potential after adoptive transfer into mouse recipients
Müller, A. M., & Dzierzak, E. A. (1993) · Development · doi:10.1242/dev.118.4.1343 · Cited by 125 · see citing works
Exit from G0 and entry into the cell cycle of cells expressing p21Sdi1 antisense RNA.
Nakanishi, M., Adami, G. R., Robetorye, R. S., Noda, A., Venable, S. F., Dimitrov, D., Pereira‐Smith, O. M., & Smith, J. R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.10.4352 · Cited by 119 · see citing works
Müller‐Sieburg, C. E., & Riblet, R. J. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.3.1141 · Cited by 109 · see citing works
Mantel, C., Luo, Z., Canfield, J., Braun, S. E., Deng, C., & Broxmeyer, H. (1996) · Blood · doi:10.1182/blood.v88.10.3710.bloodjournal88103710 · Cited by 102 · see citing works
Taniguchi, T., Endo, H., Chikatsu, N., Uchimaru, K., Asano, S., Fujita, T., Nakahata, T., & Motokura, T. (1999) · Blood · doi:10.1182/blood.v93.12.4167 · Cited by 96 · see citing works
Yaroslavskiy, B. B., Watkins, S. C., Donnenberg, A. D., Patton, T., & Steinman, R. A. (1999) · Blood · doi:10.1182/blood.v93.9.2907.409a34_2907_2917 · Cited by 76 · see citing works
Дризе, Н. И., Keller, J., & Chertkov, J. (1996) · Blood · doi:10.1182/blood.v88.8.2927.bloodjournal8882927 · Cited by 68 · see citing works
Gothot, A., Pyatt, R. E., McMahel, J., et al. (1998) · PubMed · Cited by 51 · see citing works
Grzegorzewski, K. J., Ruscetti, F. W., Usui, N., et al. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.180.3.1047 · Cited by 49 · see citing works
Braun, S. E., Mantel, C., Rosenthal, M. S., Cooper, S. H., Liu, L., Robertson, K. A., Hromas, R., & Broxmeyer, H. E. (1998) · Blood Cells Molecules and Diseases · doi:10.1006/bcmd.1998.0181 · Cited by 41 · see citing works
Gardner, R. V., Astle, C. M., & Harrison, D. E. (1997) · PubMed · Cited by 37 · see citing works
Stem cell self-renewal considerations in bone marrow transplantation.
Mauch, P., Ferrara, J. L. M., & Hellmän, S. (1989) · PubMed · Cited by 28 · see citing works
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Cited by
Sorted by citations
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
Cell cycle, CDKs and cancer: a changing paradigm
Malumbres, M., & Barbacid, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2602 · Cited by 3,957 · see citing works
p21 in cancer: Intricate networks and multiple activities
Abbas, T., & Dutta, A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2657 · Cited by 2,712 · see citing works
A role for Wnt signalling in self-renewal of haematopoietic stem cells
Reya, T., Duncan, A. W., Ailles, L., Domen, J., Scherer, D. C., Willert, K., Hintz, L., Nusse, R., & Weissman, I. L. (2003) · Nature · doi:10.1038/nature01593 · Cited by 2,159 · see citing works
Bmi-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 · see citing works
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708 · 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
IFNα activates dormant haematopoietic stem cells in vivo
Essers, M. A. G., Offner, S., Blanco-Bose, W. E., Waibler, Z., Kalinke, U., Duchosal, M. A., & Trumpp, A. (2009) · Nature · doi:10.1038/nature07815 · Cited by 1,368 · 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
Molecular regulation of stem cell quiescence
Cheung, T. H., & Rando, T. A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3591 · Cited by 1,148 · 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
Dnmt3a is essential for hematopoietic stem cell differentiation
Challen, G. A., Sun, D., Jeong, M., Luo, M., Jelinek, J., Berg, J. S., Bock, C., Vasanthakumar, A., Gu, H., Xi, Y., et al. (2012) · Nature Genetics · doi:10.1038/ng.1009 · Cited by 1,122 · see citing works
Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
Janzen, V., Forkert, R., Fleming, H. E., Saito, Y., Waring, M. T., Dombkowski, D. M., Cheng, T., DePinho, R. A., Sharpless, N. E., & Scadden, D. T. (2006) · Nature · doi:10.1038/nature05159 · Cited by 1,106 · see citing works
Self-citationTargeting p53 pathways: mechanisms, structures, and advances in therapy
Wang, H., Guo, M., Wei, H., & Chen, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01347-1 · Cited by 1,016 · see citing works
Jang, Y.-Y., & Sharkis, S. J. (2007) · Blood · doi:10.1182/blood-2007-05-087759 · Cited by 894 · see citing works
Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation
Orford, K. W., & Scadden, D. T. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2269 · Cited by 851 · see citing works
Self-citationStem 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
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
Valk-Lingbeek, M. E., Bruggeman, S. W. M., & van Lohuizen, M. (2004) · Cell · doi:10.1016/j.cell.2004.08.005 · Cited by 743 · see citing works
Chen, C., Liu, Y., Liu, R., Ikenoue, T., Guan, K.-L., Liu, Y., & Zheng, P. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20081297 · Cited by 682 · see citing works
Passegué, E., Wagers, A. J., Giuriato, S., Anderson, W. C., & Weissman, I. L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050967 · Cited by 646 · see citing works
Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells
Foudi, A., Hochedlinger, K., Van Buren, D., Schindler, J. W., Jaenisch, R., Carey, V., & Hock, H. (2009) · Nature Biotechnology · doi:10.1038/nbt.1517 · Cited by 586 · see citing works
p53 Regulates Hematopoietic Stem Cell Quiescence
Liu, Y., Elf, S. E., Miyata, Y., Sashida, G., Liu, Y., Huang, G., Di Giandomenico, S., Lee, J. M., Deblasio, A., Menendez, S., et al. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2008.11.006 · Cited by 547 · see citing works
DNA repair is limiting for haematopoietic stem cells during ageing
Nijnik, A., Woodbine, L., Marchetti, C., Dawson, S., Lambe, T., Liu, C., Rodrigues, N. P., Crockford, T. L., Cabuy, E., Vindigni, A., et al. (2007) · Nature · doi:10.1038/nature05875 · Cited by 518 · see citing works
Self-citationEnhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1
Iwama, A., Oguro, H., Negishi, M., Kato, Y., Morita, Y., Tsukui, H., Ema, H., Kamijo, T., Katoh-Fukui, Y., Koseki, H., et al. (2004) · Immunity · doi:10.1016/j.immuni.2004.11.004 · Cited by 515 · see citing works
Mira, H., Andreu, Z., Suh, H., Lie, D. C., Jessberger, S., Consiglio, A., San Emeterio, J., Hortigüela, R., Marqués-Torrejón, M. Á., Nakashima, K., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.04.016 · Cited by 480 · see citing works
Telomerase Reverse Transcriptase Delays Aging in Cancer-Resistant Mice
Tomás-Loba, A., Flores, I., Fernández-Marcos, P. J., Cayuela, M. L., Maraver, A., Tejera, A., Borrás, C., Matheu, A., Klatt, P., Flores, J. M., et al. (2008) · Cell · doi:10.1016/j.cell.2008.09.034 · Cited by 484 · see citing works
FoxOs Cooperatively Regulate Diverse Pathways Governing Neural Stem Cell Homeostasis
Paik, J.-H., Ding, Z., Narurkar, R., Ramkissoon, S., Muller, F., Kamoun, W. S., Chae, S.-S., Zheng, H., Ying, H., Mahoney, J., et al. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.09.013 · Cited by 459 · see citing works
Kippin, T. E., Martens, D. J., & van der Kooy, D. (2005) · Genes & Development · doi:10.1101/gad.1272305 · Cited by 442 · see citing works
Choudhury, A. R., Ju, Z., Djojosubroto, M. W., Schienke, A., Lechel, A., Schaetzlein, S., Jiang, H., Stepczynska, A., Wang, C., Buer, J., et al. (2007) · Nature Genetics · doi:10.1038/ng1937 · Cited by 426 · see citing works
Rb Regulates Interactions between Hematopoietic Stem Cells and Their Bone Marrow Microenvironment
Walkley, C. R., Shea, J. M., Sims, N. A., Purton, L. E., & Orkin, S. H. (2007) · Cell · doi:10.1016/j.cell.2007.03.055 · Cited by 424 · see citing works
DNA damage checkpoints in stem cells, ageing and cancer
Sperka, T., Wang, J., & Rudolph, K. L. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3420 · Cited by 393 · see citing works
Aging and disease as modifiers of efficacy of cell therapy
Dimmeler, S., & Leri, A. (2008) · Circulation Research · doi:10.1161/circresaha.108.175943 · Cited by 379 · see citing works
mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging
Castilho, R. M., Squarize, C. H., Chodosh, L. A., Williams, B. O., & Gutkind, J. S. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.06.017 · Cited by 371 · see citing works
Total body irradiation selectively induces murine hematopoietic stem cell senescence.
Wang, Y., Schulte, B. A., LaRue, A. C., Ogawa, M., & Zhou, D. (2006) · Blood · doi:10.1182/blood-2005-04-1418 · Cited by 351 · see citing works
Shamloo, B., & Usluer, S. (2019) · Cancers · doi:10.3390/cancers11081178 · Cited by 336 · see citing works
FoxO Transcription Factors and Stem Cell Homeostasis: Insights from the Hematopoietic System
Tothova, Z., & Gilliland, D. G. (2007) · Cell Stem Cell · doi:10.1016/j.stem.2007.07.017 · Cited by 331 · see citing works
p57 is required for quiescence and maintenance of adult hematopoietic stem cells
Matsumoto, A., Takeishi, S., Kanie, T., Susaki, E., Onoyama, I., Tateishi, Y., Nakayama, K., & Nakayama, K. I. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.06.014 · Cited by 329 · see citing works
Control of the Reversibility of Cellular Quiescence by the Transcriptional Repressor HES1
Sang, L., Coller, H. A., & Roberts, J. M. (2008) · Science · doi:10.1126/science.1155998 · Cited by 313 · see citing works
Kunieda, T., Minamino, T., Nishi, J.-I., Tateno, K., Oyama, T., Katsuno, T., Miyauchi, H., Orimo, M., Okada, S., Takamura, M., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.626606 · Cited by 302 · see citing works
Mitotic and mitogenic Wnt signalling
Niehrs, C., & Acebron, S. P. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.124 · Cited by 305 · see citing works
Zou, P., Yoshihara, H., Hosokawa, K., Tai, I., Shinmyozu, K., Tsukahara, F., Maru, Y., Nakayama, K., Nakayama, K. I., & Suda, T. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.07.003 · Cited by 289 · see citing works
Chaperone-mediated autophagy sustains haematopoietic stem-cell function
Dong, S., Wang, Q., Kao, Y.-R., Diaz, A., Tasset, I., Kaushik, S., Thiruthuvanathan, V., Zintiridou, A., Nieves, E., Dzieciatkowska, M., et al. (2021) · Nature · doi:10.1038/s41586-020-03129-z · Cited by 275 · see citing works
Yamazaki, S., Iwama, A., Takayanagi, S., Morita, Y., Eto, K., Ema, H., & Nakauchi, H. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601236 · Cited by 270 · see citing works
Yalcin, S., Zhang, X., Luciano, J. P., Mungamuri, S. K., Marinkovic, D., Vercherat, C., Sarkar, A., Grisotto, M., Taneja, R., & Ghaffari, S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800517200 · Cited by 247 · see citing works
Devgan, V., Mammucari, C., Millar, S. E., Brisken, C., & Dotto, G. P. (2005) · Genes & Development · doi:10.1101/gad.341405 · Cited by 209 · see citing works
Cancer and ageing: convergent and divergent mechanisms
Serrano, M., & Blasco, M. A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2242 · Cited by 182 · see citing works
Viatour, P., Somervaille, T. C., Venkatasubrahmanyam, S., Kogan, S., McLaughlin, M. E., Weissman, I. L., Butte, A. J., Passegué, E., & Sage, J. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.07.009 · Cited by 178 · see citing works
Staber, P. B., Zhang, P., Ye, M., Welner, R. S., Nombela-Arrieta, C., Bach, C., Kerenyi, M., Bartholdy, B. A., Zhang, H., Alberich-Jordà, M., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.007 · Cited by 158 · see citing works
Johnson, S. M., Torrice, C. D., Bell, J. F., Monahan, K. B., Jiang, Q., Wang, Y., Ramsey, M. R., Jin, J., Wong, K.-K., Su, L., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci41402 · Cited by 168 · see citing works
Hematopoietic Stem Cells and Their Roles in Tissue Regeneration
Lee, J. Y., & Hong, S.-H. (2020) · International Journal of Stem Cells · doi:10.15283/ijsc19127 · Cited by 165 · see citing works
DNA damage in stem cells activates p21, inhibits p53, and induces symmetric self-renewing divisions.
Insinga, A., Cicalese, A., Faretta, M., Gallo, B., Albano, L., Ronzoni, S., Furia, L., Viale, A., & Pelicci, P. G. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1213394110 · Cited by 140 · see citing works
Tang, D., Tao, S., Chen, Z., Koliesnik, I. O., Calmes, P. G., Hoerr, V., Han, B., Gebert, N., Zörnig, M., Löffler, B., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20151100 · Cited by 133 · see citing works
The p53 pathway in hematopoiesis: lessons from mouse models, implications for humans
Pant, V., Quintás-Cardama, A., & Lozano, G. (2012) · Blood · doi:10.1182/blood-2012-05-356014 · Cited by 129 · see citing works
Hematopoietic stem cell exhaustion impacted by p18INK4C and p21Cip1/Waf1 in opposite manners
Yu, H., Yuan, Y., Shen, H., & Cheng, T. (2006) · Blood · doi:10.1182/blood-2005-02-0685 · Cited by 127 · see citing works
Self-citationSun, W., & Downing, J. R. (2004) · Blood · doi:10.1182/blood-2003-12-4349 · Cited by 118 · see citing works
Cell cycle inhibitors in normal and tumor stem cells.
Cheng, T. (2004) · Oncogene · doi:10.1038/sj.onc.1207945 · Cited by 117 · see citing works
Self-citationAdult Stem Cells and Diseases of Aging
Boyette, L., & Tuan, R. (2014) · Journal of Clinical Medicine · doi:10.3390/jcm3010088 · Cited by 108 · see citing works
Unique effects of Stat3 on the early phase of hematopoietic stem cell regeneration
Chung, Y.-J., Park, B.-B., Kang, Y.-J., Kim, T.-M., Eaves, C. J., & Oh, I.-H. (2006) · Blood · doi:10.1182/blood-2006-01-010199 · Cited by 107 · see citing works
Pechnick, R. N., Zonis, S., Wawrowsky, K., Pourmorady, J., & Chesnokova, V. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711030105 · Cited by 103 · see citing works
Araki, H., Yoshinaga, K., Boccuni, P., Zhao, Y., Hoffman, R., & Mahmud, N. (2007) · Blood · doi:10.1182/blood-2006-07-035287 · Cited by 98 · see citing works
ATRX is a regulator of therapy induced senescence in human cells
Kovatcheva, M., Liao, W., Klein, M. E., Robine, N., Geiger, H., Crago, A. M., Dickson, M. A., Tap, W. D., Singer, S., & Koff, A. (2017) · Nature Communications · doi:10.1038/s41467-017-00540-5 · Cited by 89 · see citing works
Beier, F., Foronda, M., Martinez, P., & Blasco, M. A. (2012) · Blood · doi:10.1182/blood-2012-03-418038 · Cited by 79 · see citing works
Ohtani, N., Imamura, Y., Yamakoshi, K., Hirota, F., Nakayama, R., Kubo, Y., Ishimaru, N., Takahashi, A., Hirao, A., Shimizu, T., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706949104 · Cited by 73 · see citing works
Walkley, C. R., & Orkin, S. H. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603389103 · Cited by 71 · see citing works
Stepanova, L., & Sorrentino, B. P. (2005) · Blood · doi:10.1182/blood-2004-06-2242 · Cited by 68 · see citing works
Shen, H., Yu, H., Liang, P. H., Cheng, H., XuFeng, R., Yuan, Y., Zhang, P., Smith, C. A., & Cheng, T. (2012) · Blood · doi:10.1182/blood-2011-08-373621 · Cited by 62 · see citing works
Self-citationJeong, M., Piao, Z.-H., Kim, M. S., Lee, S. H., Yun, S., Sun, H.-N., Yoon, S. R., Chung, J. W., Kim, T.-D., Jeon, J. H., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0804221 · Cited by 58 · see citing works
Wang, Y. V., Leblanc, M., Fox, N., Mao, J.-H., Tinkum, K. L., Krummel, K., Engle, D., Piwnica-Worms, D., Piwnica-Worms, H., Balmain, A., et al. (2011) · Genes & Development · doi:10.1101/gad.2024411 · Cited by 53 · see citing works
Daria, D., Filippi, M.-D., Knudsen, E. S., Faccio, R., Li, Z., Kalfa, T., & Geiger, H. (2008) · Blood · doi:10.1182/blood-2007-02-071746 · Cited by 46 · see citing works
Adult Stem Cells Exhibit Global Suppression of RNA Polymerase II Serine-2 Phosphorylation
Freter, R., Osawa, M., & Nishikawa, S.-I. (2010) · Stem Cells · doi:10.1002/stem.476 · Cited by 43 · see citing works
Foxo3a is essential for maintenance of the hematopoietic stem cell pool.
Miyamoto, K., Araki, K. Y., Naka, K., Arai, F., Takubo, K., Yamazaki, S., Matsuoka, S., Miyamoto, T., Ito, K., Ohmura, M., et al. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.02.001 · Cited by 41 · see citing works
ATP-dependent chromatin remodelers in ageing and age-related disorders
Swer, P. B., & Sharma, R. (2021) · Biogerontology · doi:10.1007/s10522-020-09899-3 · Cited by 25 · see citing works
The Therapeutic Potential of Hematopoietic Stem Cells in Bone Regeneration
Oliveira, C. S., Carreira, M., Correia, C. R., & Mano, J. F. (2022) · Tissue Engineering Part B: Reviews · doi:10.1089/ten.teb.2021.0019 · Cited by 14 · see citing works
- Authors
- Cheng, T., Rodrigues, N., Shen, H., Yang, Y.-G., Dombkowski, D., Sykes, M., & Scadden, D. T.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Scadden, David T.
- Venue
- Science
- Published
- 2000-03-10
- Volume
- 287
- Issue
- 5459
- Pages
- 1804-1808
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2093958228
- Cited by
- 1,339
- References
- 35
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 18 · 2023: 26 · 2022: 35 · 2021: 34 · 2020: 28 · 2019: 33 · 2018: 32 · 2017: 33 · 2016: 48 · 2015: 57 · 2014: 58 · 2013: 74 · 2012: 63
- FWCI
- 22.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL044851, HL44851)
- National Institute of Allergy and Infectious Diseases (AI 07387, T32AI007387)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK50234, R01DK050234)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- hematopoietic stem cells, stem cell quiescence, p21, cyclin-dependent kinase inhibitors, G1/S checkpoint, stem cell self-renewal, stem cell proliferation, myelosuppression, hematopoietic failure, stem cell exhaustion, bone marrow transplantation
- MeSH terms
- Animals, Antimetabolites, Blood Cell Count, Cell Count, Cell Cycle, Cell Differentiation, Cell Division, Colony-Forming Units Assay, Female, Fluorouracil, Hematopoiesis, Hematopoietic Stem Cells, Homeostasis, Male, Mice, Inbred Strains, Bone Marrow Transplantation, Cyclins, Cell Death, Coculture Techniques, Cyclin-Dependent Kinase Inhibitor p21, Mice
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