A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells
Open accessAbstract
Whether hematopoietic stem cells (HSCs) change with aging has been controversial. Previously, we showed that the HSC compartment in young mice consists of distinct subsets, each with predetermined self-renewal and differentiation behavior. Three classes of HSCs can be distinguished based on their differentiation programs: lymphoid biased, balanced, and myeloid biased. We now show that aging causes a marked shift in the representation of these HSC subsets. A clonal analysis of repopulating HSCs demonstrates that lymphoid-biased HSCs are lost and long-lived myeloid-biased HSCs accumulate in the aged. Myeloid-biased HSCs from young and aged sources behave similarly in all aspects tested. This indicates that aging does not change individual HSCs. Rather, aging changes the clonal composition of the HSC compartment. We show further that genetic factors contribute to the age-related changes of the HSC subsets. In comparison with B6 mice, aged D2 mice show a more pronounced shift toward myeloid-biased HSCs with a corresponding reduction in the number of both T- and B-cell precursors. This suggests that low levels of lymphocytes in the blood can be a marker for HSC aging. The loss of lymphoid-biased HSCs may contribute to the impaired immune response to infectious diseases and cancers in the aged.
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?
The number of lymphoid-biased stem cells decreases with age while myeloid-biased hematopoietic stem cells increase.
“it is now appreciated that the number of lymphoid-biased stem cells declines with age concomitant with an increase in myeloid-biased HSCs (19).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [19]
Aged mice have an overall larger HSC pool.
“in aged mice that display an overall increase in HSC pool size”
From Aging of hematopoietic stem cells (2018) · cites this paper as [32]
The functional heterogeneity of the HSC population rises with age.
“the functional heterogeneity of the HSC population increases with age.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [32]
Individual HSCs in aged mice behave very differently from one another.
“individual HSCs behave very differently.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [32]
Mice whose blood cell production comes from even a single stem cell are not necessarily prone to leukemia.
“mice in which blood cell production is derived from even a single stem cell, are not necessarily prone to develop leukemia.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [32]
Donor-derived reconstitution from old HSCs is significantly lower than from young HSCs and shows a marked myeloid bias.
“examination of donor-derived reconstitution from old HSCs was significantly lower compared to the young with a marked myeloid bias lineage output”
From Quiescent Hematopoietic Stem Cells Accumulate DNA Damage during Aging that Is Repaired upon Entry into Cell Cycle (2014) · cites this paper as Cho 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
Cell intrinsic alterations underlie hematopoietic stem cell aging
Rossi, D. J., Bryder, D., Zahn, J. M., Ahlenius, H., Sonu, R., Wagers, A. J., & Weissman, I. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503280102 · Cited by 1,152 · cited 1× · see citing works
“For example, aged HSCs may have a reduced ability to home to the bone marrow (BM),(5,6) an altered cell surface phenotype,(5,7) may cycle more rapidly,(5) produce more myeloid cells,(5-8) and have a different gene expression program than their young counterparts.(9,10) HSCs from aged environments may have slightly les…”
BackgroundDeficiencies in DNA damage repair limit the function of haematopoietic stem cells with age
Rossi, D. J., Bryder, D., Seita, J., Nussenzweig, A., Hoeijmakers, J., & Weissman, I. L. (2007) · Nature · doi:10.1038/nature05862 · Cited by 1,115 · 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
The aging of hematopoietic stem cells
Morrison, S. J., Wandycz, A. M., Akashi, K., Globerson, A., & Weissman, I. L. (1996) · Nature Medicine · doi:10.1038/nm0996-1011 · Cited by 853 · see citing works
Aging Hematopoietic Stem Cells Decline in Function and Exhibit Epigenetic Dysregulation
Chambers, S. M., Shaw, C. A., Gatza, C. E., Fisk, C. J., Donehower, L. A., & Goodell, M. A. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050201 · Cited by 799 · see citing works
Age-Associated Characteristics of Murine Hematopoietic Stem Cells
Sudo, K., Ema, H., Morita, Y., & Nakauchi, H. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.9.1273 · Cited by 722 · see citing works
Long-Term Propagation of Distinct Hematopoietic Differentiation Programs In Vivo
Dykstra, B. J., Kent, D. G., Bowie, M. B., McCaffrey, L., Hamilton, M. J., Lyons, K., Lee, S.-J., Brinkman, R. R., & Eaves, C. J. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.05.015 · Cited by 632 · see citing works
Clonal and systemic analysis of long-term hematopoiesis in the mouse.Preprint
Jordan, C. T., & Lemischka, I. R. (1990) · Genes & Development · doi:10.1101/gad.4.2.220 · Cited by 566 · 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
Szilvassy, S. J., Humphries, R. K., Lansdorp, P. M., Eaves, A. C., & Eaves, C. J. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.22.8736 · Cited by 450 · see citing works
Reversible Expression of CD34 by Murine Hematopoietic Stem Cells
Sato, T., Laver, J. H., & Ogawa, M. (1999) · Blood · doi:10.1182/blood.v94.8.2548.420k38_2548_2554 · Cited by 393 · see citing works
Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells
Liang, Y., Zant, G. E. V., & Szilvassy, S. J. (2005) · Blood · doi:10.1182/blood-2004-11-4282 · Cited by 384 · see citing works
de Haan, G., NIJHOF, W., & Zant, G. E. V. (1997) · Blood · doi:10.1182/blood.v89.5.1543 · Cited by 300 · see citing works
Müller‐Sieburg, C. E., Cho, R. H., Karlsson, L., Huang, J.-F., & Sieburg, H. B. (2004) · Blood · doi:10.1182/blood-2003-10-3448 · Cited by 284 · see citing works
Self-citationDeterministic regulation of hematopoietic stem cell self-renewal and differentiation
Müller‐Sieburg, C. E., Cho, R. H., Thoman, M. L., Adkins, B., & Sieburg, H. B. (2002) · Blood · doi:10.1182/blood.v100.4.1302.h81602001302_1302_1309 · Cited by 282 · see citing works
Self-citationHarrison, D. E., Jordan, C. T., Zhong, R. K., & Astle, C. M. (1993) · PubMed · Cited by 273 · see citing works
Yilmaz, Ö. H., Kiel, M. J., & Morrison, S. J. (2005) · Blood · doi:10.1182/blood-2005-05-2140 · Cited by 266 · see citing works
The Decline in B Lymphopoiesis in Aged Mice Reflects Loss of Very Early B-Lineage Precursors
Miller, J. P., & Allman, D. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.5.2326 · Cited by 255 · see citing works
The hematopoietic stem compartment consists of a limited number of discrete stem cell subsets
Sieburg, H. B., Cho, R. H., Dykstra, B. J., Uchida, N., Eaves, C. J., & Müller‐Sieburg, C. E. (2005) · Blood · doi:10.1182/blood-2005-07-2970 · Cited by 236 · see citing works
Self-citationThe aging of lympho-hematopoietic stem cells
Geiger, H., & Van Zant, G. (2002) · Nature Immunology · doi:10.1038/ni0402-329 · Cited by 233 · see citing works
Telomerase Activity in Candidate Stem Cells From Fetal Liver and Adult Bone Marrow
Yui, J., Chiu, C.-P., & Lansdorp, P. M. (1998) · Blood · doi:10.1182/blood.v91.9.3255 · Cited by 216 · see citing works
Numbers and functions of transplantable primitive immunohematopoietic stem cells. Effects of age.
Harrison, D. E., Astle, C. M., & Stone, M. (1989) · The Journal of Immunology · doi:10.4049/jimmunol.142.11.3833 · Cited by 148 · see citing works
Bone marrow cells give rise to distinct cell clones within the thymus
Ezine, S., Weissman, I. L., & Rouse, R. V. (1984) · Nature · doi:10.1038/309629a0 · Cited by 143 · see citing works
Major Age‐Related Changes Of Mouse Hematopoietic Stem/Progenitor Cells
KIM, M., Moon, H., & Spangrude, G. J. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb03247.x · Cited by 142 · see citing works
Andrew, D., & Aspinall, R. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.3.1524 · Cited by 138 · see citing works
Intrinsic and extrinsic control of hemopoietic stem cell numbers: mapping of a stem cell gene
Haan, G. D., & Zant, G. V. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.4.529 · Cited by 134 · see citing works
Stephan, R. P., Lill-Elghanian, D. A., & Witte, P. L. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.4.1598 · Cited by 133 · see citing works
Genetic regulation of primitive hematopoietic stem cell senescence
Chen, J., Astle, C. M., & Harrison, D. E. (2000) · Experimental Hematology · doi:10.1016/s0301-472x(99)00157-5 · Cited by 131 · see citing works
Impaired hematopoietic stem cell functioning after serial transplantation and during normal aging
Kamminga, L. M., van Os, R., Ausema, A., Noach, E. J. K., Weersing, E., Dontje, B., Vellenga, E., & de Haan, G. (2005) · STEM CELLS · doi:10.1634/stemcells.2004-0066 · Cited by 128 · see citing works
Hematopoietic stem cells do not engraft with absolute efficiencies
Camargo, F. D., Chambers, S. M., Drew, E., McNagny, K. M., & Goodell, M. A. (2005) · Blood · doi:10.1182/blood-2005-02-0655 · Cited by 125 · see citing works
Normal Production of Erythrocytes by Mouse Marrow Continuous for 73 Months
Harrison, D. E. (1973) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.70.11.3184 · Cited by 123 · 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
Uchida, N., Dykstra, B. J., Lyons, K., Leung, F. Y. K., & Eaves, C. J. (2003) · Experimental Hematology · doi:10.1016/j.exphem.2003.09.001 · Cited by 108 · see citing works
Age- and stage-specific regulation patterns in the hematopoietic stem cell hierarchy
Geiger, H., True, J. M., de Haan, G., & Zant, G. E. V. (2001) · Blood · doi:10.1182/blood.v98.10.2966 · Cited by 103 · see citing works
Van Zant, G., Holland, B. P., Eldridge, P. W., & Chen, J. J. (1990) · The Journal of Experimental Medicine · doi:10.1084/jem.171.5.1547 · Cited by 99 · cited 1× · see citing works
“That HSCs in D2 and B6 mice age differently had been established in an elegant series of experiments that followed D2 and B6 HSCs in aggregation chimeras.(58) In a subset of these chimeras, D2 HSCs stopped to contribute to peripheral hematopoiesis when mice aged.”
BackgroundLiang, Y., Jansen, M., Aronow, B. J., Geiger, H., & Zant, G. E. V. (2007) · Nature Genetics · doi:10.1038/ng1938 · Cited by 97 · see citing works
Linton, P. (2001) · Frontiers in bioscience · doi:10.2741/linton · Cited by 97 · see citing works
Zhong, R. K., Astle, C. M., & Harrison, D. E. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.1.138 · Cited by 94 · see citing works
Two rare populations of mouse Thy-1lo bone marrow cells repopulate the thymus.
Spangrude, G. J., Müller‐Sieburg, C. E., Heimfeld, S., & Weissman, I. L. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.167.5.1671 · Cited by 92 · see citing works
Marley, Lewis, Davidson, Roberts, Dokal, I. S., Goldman, & Gordon (1999) · British Journal of Haematology · doi:10.1046/j.1365-2141.1999.01477.x · Cited by 90 · see citing works
An X chromosome gene regulates hematopoietic stem cell kinetics
Abkowitz, J. L., Taboada, M. R., Shelton, G. H., Catlin, S. N., Guttorp, P. M., & Kiklevich, J. V. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3862 · Cited by 90 · see citing works
Wineman, J., Nishikawa, S., & Muller-Sieburg, C. (1993) · Blood · doi:10.1182/blood.v81.2.365.365 · Cited by 87 · see citing works
Self-citationINNES, J. (1949) · PubMed · Cited by 83 · see citing works
Independent homeostatic regulation of B cell compartments
Agenès, F., Rosado, M. M., & Freitas, A. A. (1997) · European Journal of Immunology · doi:10.1002/eji.1830270731 · Cited by 80 · see citing works
Trevisan, M., Yan, X., & Iscove, N. (1996) · Blood · doi:10.1182/blood.v88.11.4149.4149 · Cited by 65 · see citing works
Regulation of hematopoietic stem cell aging in vivo by a distinct genetic element
Geiger, H., Rennebeck, G., & Zant, G. E. V. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408654102 · Cited by 61 · see citing works
Hematopoiesis in the aged: a model of hematopoietic dysregulation? [editorial; comment]
Rothstein, G. (1993) · Blood · doi:10.1182/blood.v82.9.2601.2601 · Cited by 52 · see citing works
Henckaerts, E., Langer, J., & Snoeck, H. (2004) · Blood · doi:10.1182/blood-2003-12-4304 · Cited by 52 · see citing works
Linking age-related defects in B lymphopoiesis to the aging of hematopoietic stem cells
Miller, J. P., & Allman, D. (2005) · Seminars in Immunology · doi:10.1016/j.smim.2005.05.003 · Cited by 50 · see citing works
Early Steps in T Cell Development Are Affected by Aging
Thoman, M. L. (1997) · Cellular Immunology · doi:10.1006/cimm.1997.1133 · Cited by 46 · see citing works
Mühlethaler‐Mottet, A., Bourloud, K. B., Auderset, K., Joseph, J., & Groß, N. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1299.033 · Cited by 44 · see citing works
Clonal diversity of the stem cell compartment
Müller‐Sieburg, C. E., & Sieburg, H. B. (2006) · Current Opinion in Hematology · doi:10.1097/01.moh.0000231421.00407.65 · Cited by 40 · see citing works
Self-citationCho, R. H., & Müller‐Sieburg, C. E. (2000) · Experimental Hematology · doi:10.1016/s0301-472x(00)00507-5 · Cited by 38 · see citing works
Self-citationLymphoid and erythroid repopulation in B6 W-anemic mice: a new unirradiated recipient.
Harrison, D. E., & Astle, C. M. (1991) · PubMed · Cited by 37 · see citing works
Quantitative analysis of bone marrow thymic progenitors in young and aged mice
Eren, R., Globerson, A., Abel, L., & Zharhary, D. (1990) · Cellular Immunology · doi:10.1016/0008-8749(90)90129-f · Cited by 36 · see citing works
Maximum Life Spans in Mice are Extended by Wild Strain Alleles
Klebanov, S., Astle, C. M., Roderick, T. H., Flurkey, K., Archer, J. R., & Chen, J. (2001) · Experimental Biology and Medicine · doi:10.1177/153537020122600908 · Cited by 33 · see citing works
Sherwood, E. R. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(02)00042-8 · Cited by 30 · see citing works
Impaired Thymic Regeneration in Lethally Irradiated Mice Given Bone Marrow from Aged Donors
Tyan, M. L. (1976) · Experimental Biology and Medicine · doi:10.3181/00379727-152-39321 · Cited by 26 · see citing works
Hsu, H., Mountz, J. D., Williams, R. W., Shelton, B. J., Yang, P., Matsuki, Y., Xu, X., Dodd, C. H., Li, L., Geiger, H., et al. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(02)00004-0 · Cited by 23 · see citing works
Nakano, T., Waki, N., Asai, H., & Kitamura, Y. (1989) · Blood · doi:10.1182/blood.v73.2.425.425 · Cited by 17 · see citing works
Genetic Dissection of Age‐Related Changes of Immune Function in Mice
Mountz, J. D., Zant, G. E. V., Zhang, H., Grizzle, W. E., Ahmed, R., Williams, R. W., & Hsu, H. (2001) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.2001.00943.x · Cited by 14 · see citing works
Flagged first, then by citations
1 of the 62 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Sudo K, Ema H, Morita Y, Nakauchi H. Age-as- sociated characteristics of murine hematopoi- etic stem cells. J Exp Med. 2000;192:1273- 1280.
- Chen J, Astle CM, Harrison DE. Genetic regula- tion of primitive hematopoietic stem cell senes- cence. Exp Hematol. 2000;28:442-450.
Cited by
Sorted by citations
Age-dependent dysregulation of innate immunity
Shaw, A. C., Goldstein, D. R., & Montgomery, R. R. (2013) · Nature Reviews Immunology · doi:10.1038/nri3547 · Cited by 1,061 · see citing works
Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age
Pang, W. W., Price, E. A., Sahoo, D., Beerman, I., Maloney, W. J., Rossi, D. J., Schrier, S. L., & Weissman, I. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116110108 · Cited by 991 · see citing works
Haematopoietic stem cell activity and interactions with the niche
Pinho, S., & Frenette, P. S. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0103-9 · Cited by 990 · see citing works
Causes, consequences, and reversal of immune system aging
Montecino-Rodriguez, E., Berent-Maoz, B., & Dorshkind, K. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64096 · Cited by 793 · see citing works
Beerman, I., Bhattacharya, D., Zandi, S., Sigvardsson, M., Weissman, I. L., Bryder, D., & Rossi, D. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000834107 · Cited by 711 · see citing works
Sun, D., Luo, M., Jeong, M., Rodriguez, B., Xia, Z., Hannah, R., Wang, H., Le, T., Faull, K. F., Chen, R., et al. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.03.002 · Cited by 686 · see citing works
Distinct Hematopoietic Stem Cell Subtypes Are Differentially Regulated by TGF-β1
Challen, G. A., Boles, N. C., Chambers, S. M., & Goodell, M. A. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.02.002 · Cited by 580 · see citing works
Immune cell dysfunction and inflammation in end-stage renal disease
Betjes, M. G. H. (2013) · Nature Reviews Nephrology · doi:10.1038/nrneph.2013.44 · Cited by 552 · see citing works
Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells
Dykstra, B., Olthof, S., Schreuder, J., Ritsema, M., & de Haan, G. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20111490 · Cited by 494 · see citing works
“Specifically, myeloid-dominant HSCs are thought to accumulate in the old HSC pool at the expense of lymphoid-dominant and lineage-balanced HSCs (Cho et al., 2008; Muller-Sieburg and Sieburg, 2008; Beerman et al., 2010a; Challen et al., 2010).”
BackgroundInfluentialCheng, C., Adams, G. B., Perin, L., Wei, M., Zhou, X., Lam, B. S., Sacco, S. D., Mirisola, M. G., Quinn, D. I., Dorff, T. B., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.04.014 · Cited by 484 · see citing works
The immune system and aging: A review
Castelo-Branco, C., & Soveral, I. (2014) · Gynecological Endocrinology · doi:10.3109/09513590.2013.852531 · Cited by 449 · see citing works
Taurine deficiency as a driver of aging
Singh, P. P., Gollapalli, K., Mangiola, S., Schranner, D., Yusuf, M. A., Chamoli, M., Shi, S. L., Lopes-Bastos, B., Nair, T., Riermeier, A., et al. (2023) · Science · doi:10.1126/science.abn9257 · Cited by 447 · see citing works
Cell cycle regulation in hematopoietic stem cells
Pietras, E. M., Warr, M. R., & Passegué, E. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102131 · Cited by 447 · see citing works
Beerman, I., Seita, J., Inlay, M. A., Weissman, I. L., & Rossi, D. J. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.04.016 · Cited by 445 · see citing works
Lu, R., Neff, N. F., Quake, S. R., & Weissman, I. L. (2011) · Nature Biotechnology · doi:10.1038/nbt.1977 · Cited by 438 · see citing works
Aging of hematopoietic stem cells
de Haan, G., & Lazare, S. S. (2018) · Blood · doi:10.1182/blood-2017-06-746412 · Cited by 432 · 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
Inflamm-aging of hematopoiesis, hematopoietic stem cells, and the bone marrow microenvironment
Kovtonyuk, L. V., Fritsch, K., Feng, X., Manz, M. G., & Takizawa, H. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00502 · Cited by 371 · see citing works
A Differentiation Checkpoint Limits Hematopoietic Stem Cell Self-Renewal in Response to DNA Damage
Wang, J., Sun, Q., Morita, Y., Jiang, H., Groß, A., Lechel, A., Hildner, K., Guachalla, L. M., Gompf, A., Hartmann, D., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.040 · Cited by 343 · see citing works
CD41 expression marks myeloid-biased adult hematopoietic stem cells and increases with age
Gekas, C., & Graf, T. (2013) · Blood · doi:10.1182/blood-2012-09-457929 · Cited by 339 · see citing works
Grover, A., Sanjuán-Pla, A., Thongjuea, S., Carrelha, J., Giustacchini, A., Gambardella, A. R., Macaulay, I. C., Mancini, E., Luis, T. C., Mead, A. J., et al. (2016) · Nature Communications · doi:10.1038/ncomms11075 · Cited by 339 · see citing works
Feldman, A. L., Arber, D. A., Pittaluga, S., Martı́nez, A., Burke, J. S., Raffeld, M. A., Camós, M., Warnke, R. A., & Jaffe, E. S. (2008) · Blood · doi:10.1182/blood-2007-11-124792 · Cited by 333 · see citing works
When stem cells grow old: phenotypes and mechanisms of stem cell aging
Schultz, M. B., & Sinclair, D. A. (2016) · Development · doi:10.1242/dev.130633 · Cited by 331 · see citing works
Causes and Consequences of Hematopoietic Stem Cell Heterogeneity
Haas, S. F., Trumpp, A., & Milsom, M. D. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.04.003 · Cited by 330 · see citing works
Chronic Exposure to a TLR Ligand Injures Hematopoietic Stem Cells
Esplin, B. L., Shimazu, T., Welner, R. S., Garrett, K. P., Nie, L., Zhang, Q., Humphrey, M. B., Yang, Q., Borghesi, L., & Kincade, P. W. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003438 · Cited by 327 · see citing works
Benz, C., Copley, M. R., Kent, D. G., Wöhrer, S., Cortés, A., Aghaeepour, N., Ma, E., Mader, H., Rowe, K. M., Day, C. W., et al. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.02.007 · Cited by 322 · see citing works
Aging, inflammation, immunity and periodontal disease
Ebersole, J. L., Graves, C. L., González, O. A., Dawson, D. R., Morford, L. A., Emecen‐Huja, P., Hartsfield, J. K., Huja, S. S., Pandruvada, S. N. M., & Wallet, S. M. (2016) · Periodontology 2000 · doi:10.1111/prd.12135 · Cited by 308 · see citing works
Manifestations and mechanisms of stem cell aging
Liu, L. A., & Rando, T. A. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201010131 · Cited by 306 · see citing works
Reduced Expression of MYC Increases Longevity and Enhances Healthspan
Hofmann, J. W., Zhao, X., De Cecco, M., Peterson, A. L., Pagliaroli, L., Manivannan, J., Hubbard, G. B., Ikeno, Y., Zhang, Y., Feng, B., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.016 · Cited by 293 · see citing works
Hematopoietic stem cells count and remember self-renewal divisions
Bernitz, J. M., Kim, H. S., MacArthur, B., Sieburg, H., & Moore, K. (2016) · Cell · doi:10.1016/j.cell.2016.10.022 · Cited by 285 · see citing works
Self-citationCharacterization of bone marrow-derived mesenchymal stem cells in aging
Baker, N., Boyette, L. B., & Tuan, R. S. (2014) · Bone · doi:10.1016/j.bone.2014.10.014 · Cited by 281 · see citing works
Emerging models and paradigms for stem cell ageing
Jones, D. L., & Rando, T. A. (2011) · Nature Cell Biology · doi:10.1038/ncb0511-506 · Cited by 256 · see citing works
Lineage-Biased Hematopoietic Stem Cells Are Regulated by Distinct Niches
Pinho, S., Marchand, T., Yang, E. M., Wei, Q., Nerlov, C., & Frenette, P. S. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.01.016 · Cited by 235 · see citing works
Ageing and the immune system: focus on macrophages
Linehan, E., & Fitzgerald, D. (2015) · European Journal of Microbiology and Immunology · doi:10.1556/eujmi-d-14-00035 · Cited by 228 · see citing works
Immunosenescence, aging and successful aging
Wang, Y., Chen, D., Han, Y., Gu, Z., & Sun, C. C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.942796 · Cited by 216 · see citing works
Impact of genomic damage and ageing on stem cell function
Behrens, A., van Deursen, J. M., Rudolph, K. L., & Schumacher, B. (2014) · Nature Cell Biology · doi:10.1038/ncb2928 · Cited by 207 · see citing works
Stem cells and the aging hematopoietic system
Beerman, I., Maloney, W. J., Weissman, I. L., & Rossi, D. J. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.06.007 · Cited by 206 · see citing works
The multifaceted role of autophagy in cancer and the microenvironment
Folkerts, H., Hilgendorf, S., Vellenga, E., Bremer, E., & Wiersma, V. R. (2018) · Medicinal Research Reviews · doi:10.1002/med.21531 · Cited by 201 · see citing works
The aging skin microenvironment dictates stem cell behavior
Ge, Y., Miao, Y., Gur-Cohen, S., Gomez, N., Yang, H., Nikolova, M., Polak, L., Hu, Y., Verma, A., Elemento, O., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1901720117 · Cited by 190 · see citing works
B Cell Dysfunction Associated With Aging and Autoimmune Diseases
Ma, S., Wang, C., Mao, X., & Hao, Y. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00318 · Cited by 184 · see citing works
Hematopoiesis and Cardiovascular Disease
Poller, W. C., Nahrendorf, M., & Świrski, F. K. (2020) · Circulation Research · doi:10.1161/circresaha.120.315895 · Cited by 183 · see citing works
Verovskaya, E. V., Broekhuis, M., Zwart, E., Ritsema, M., van Os, R. P., de Haan, G., & Bystrykh, L. V. (2013) · Blood · doi:10.1182/blood-2013-01-481135 · Cited by 175 · see citing works
Immunosenescence: Aging and Immune System Decline
Goyani, P., Christodoulou, R. C., & Vassiliou, E. K. (2024) · Vaccines · doi:10.3390/vaccines12121314 · Cited by 177 · see citing works
Hematopoietic Stem Cell Heterogeneity Takes Center Stage
Copley, M. R., Beer, P. A., & Eaves, C. J. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.05.006 · Cited by 174 · see citing works
TNF Drives Monocyte Dysfunction with Age and Results in Impaired Anti-pneumococcal Immunity
Puchta, A., Naidoo, A., Verschoor, C. P., Loukov, D., Thevaranjan, N., Mandur, T. S., Nguyen, P.-S., Jordana, M., Loeb, M. B., Xing, Z., et al. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005368 · Cited by 173 · see citing works
Derhovanessian, E., Solana, R., Larbi, A., & Pawelec, G. (2008) · Immunity & Ageing · doi:10.1186/1742-4933-5-11 · Cited by 169 · see citing works
B cell maintenance and function in aging
Kogut, I., Scholz, J. L., Cancro, M. P., & Cambier, J. C. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.004 · Cited by 166 · see citing works
Stem cell heterogeneity: implications for aging and regenerative medicine
Müller‐Sieburg, C. E., Sieburg, H. B., Bernitz, J. M., & Cattarossi, G. (2012) · Blood · doi:10.1182/blood-2011-12-376749 · Cited by 164 · see citing works
Self-citationImmunosenescence and inflammaging: Mechanisms and role in diseases
Ajoolabady, A., Praticò, D., Tang, D., Zhou, S., Franceschi, C., & Ren, J. T. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102540 · Cited by 160 · see citing works
Warfvinge, R., Geironson, L., Sommarin, M. N. E., Lang, S., Karlsson, C., Roschupkina, T., Stenke, L., Stentoft, J., Olsson-Strömberg, U., Hjorth-Hansen, H., et al. (2017) · Blood · doi:10.1182/blood-2016-07-728873 · Cited by 154 · see citing works
Functional dysregulation of stem cells during aging: a focus on skeletal muscle stem cells
García‐Prat, L., Sousa‐Victor, P., & Muñoz‐Cánoves, P. (2013) · The FEBS Journal · doi:10.1111/febs.12221 · Cited by 152 · see citing works
Heterogeneity and hierarchy of hematopoietic stem cells
Ema, H., Morita, Y., & Suda, T. (2013) · Experimental Hematology · doi:10.1016/j.exphem.2013.11.004 · Cited by 150 · see citing works
Nilsson, A. R., Soneji, S., Adolfsson, S., Bryder, D., & Pronk, C. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158369 · Cited by 149 · see citing works
Cell Therapy, a New Standard in Management of Chronic Critical Limb Ischemia and Foot Ulcer
Procházka, V., Gumulec, J., Jalůvka, F., Šalounová, D., Jonszta, T., Czerný, D., Krajča, J., Urbanec, R., Klement, P., Martinek, J., et al. (2010) · Cell Transplantation · doi:10.3727/096368910x514170 · Cited by 147 · see citing works
Neutrophils in aging and aging‐related pathologies
Avondt, K. V., Strecker, J., Tulotta, C., Minnerup, J., Schulz, C., & Soehnlein, O. (2022) · Immunological Reviews · doi:10.1111/imr.13153 · Cited by 147 · see citing works
Endothelial transplantation rejuvenates aged hematopoietic stem cell function
Poulos, M. G., Ramalingam, P., Gutkin, M. C., Llanos, P., Gilleran, K., Rabbany, S. Y., & Butler, J. M. (2017) · Journal of Clinical Investigation · doi:10.1172/jci93940 · Cited by 144 · see citing works
Age-related mutations and chronic myelomonocytic leukemia
Mason, C. C., Khorashad, J. S., Tantravahi, S. K., Kelley, T. W., Zabriskie, M. S., Yan, D., Pomicter, A. D., Reynolds, K. R., Eiring, A. M., Kronenberg, Z. N., et al. (2015) · Leukemia · doi:10.1038/leu.2015.337 · Cited by 136 · see citing works
Cruickshank, M. N., Oshlack, A., Theda, C., Davis, P. G., Martino, D., Sheehan, P. M., Dai, Y., Saffery, R., Doyle, L. W., & Craig, J. M. (2013) · Genome Medicine · doi:10.1186/gm500 · Cited by 132 · see citing works
Epigenetic regulation of aging stem cells
Pollina, E. A., & Brunet, A. (2011) · Oncogene · doi:10.1038/onc.2011.45 · Cited by 128 · see citing works
Age-associated changes in human hematopoietic stem cells
Pang, W. W., Schrier, S. L., & Weissman, I. L. (2016) · Seminars in Hematology · doi:10.1053/j.seminhematol.2016.10.004 · Cited by 122 · see citing works
Valletta, S., Thomas, A., Meng, Y., Ren, X., Drissen, R., Sengül, H., Di Genua, C., & Nerlov, C. (2020) · Nature Communications · doi:10.1038/s41467-020-17942-7 · Cited by 122 · see citing works
Rheumatoid Arthritis: A Role for Immunosenescence?
Lindström, T. M., & Robinson, W. H. (2010) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2010.02965.x · Cited by 122 · see citing works
Clonal hematopoiesis and inflammation: Partners in leukemogenesis and comorbidity
Cook, E. K., Luo, M., & Rauh, M. J. (2020) · Experimental Hematology · doi:10.1016/j.exphem.2020.01.011 · Cited by 121 · see citing works
Block, T. J., Marinkovic, M., Tran, O. N., Gonzalez, A. O., Marshall, A., Dean, D. D., & Chen, X. (2017) · Stem Cell Research & Therapy · doi:10.1186/s13287-017-0688-x · Cited by 116 · see citing works
Immunoaging induced by hematopoietic stem cell aging
Wang, J., Geiger, H., & Rudolph, K. L. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.05.004 · Cited by 107 · see citing works
Kidney Transplantation in the Elderly
Huang, E., Segev, D. L., & Rabb, H. (2009) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2009.07.011 · Cited by 107 · see citing works
Sharma, G., Hanania, N. A., & Shim, Y. M. (2009) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200904-022rm · Cited by 105 · see citing works
Cheung, A. M. S., Nguyen, L. V., Carles, A., Beer, P. A., Miller, P. H., Knapp, D. J. H. F., Dhillon, K., Hirst, M., & Eaves, C. J. (2013) · Blood · doi:10.1182/blood-2013-06-508432 · Cited by 105 · see citing works
Vimentin Coordinates Protein Turnover at the Aggresome during Neural Stem Cell Quiescence Exit
Morrow, C. S., Porter, T. J., Xu, N., Arndt, Z. P., Ako-Asare, K., Heo, H. J., Thompson, E. A. N., & Moore, D. L. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.01.018 · Cited by 105 · see citing works
B-cell depletion reactivates B lymphopoiesis in the BM and rejuvenates the B lineage in aging
Keren, Z., Naor, S., Nussbaum, S., Golan, K., Itkin, T., Sasaki, Y., Schmidt-Supprian, M., Lapidot, T., & Melamed, D. (2011) · Blood · doi:10.1182/blood-2010-09-307983 · Cited by 100 · see citing works
Chronic inflammation and aging: DNA damage tips the balance
Cavanagh, M. M., Weyand, C. M., & Goronzy, J. J. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.04.003 · Cited by 99 · see citing works
Inhibition of B Lymphopoiesis by Adipocytes and IL-1–Producing Myeloid-Derived Suppressor Cells
Kennedy, D. E., & Knight, K. L. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500957 · Cited by 97 · see citing works
BMP signalling differentially regulates distinct haematopoietic stem cell types
Crisan, M., Kartalaei, P. S., Vink, C. S., Yamada-Inagawa, T., Bollérot, K., van IJcken, W. F. J., van der Linden, R., Lopes, S. M. C. D. S., Monteiro, R. M., Mummery, C. L., et al. (2015) · Nature Communications · doi:10.1038/ncomms9040 · Cited by 95 · see citing works
Lifelong haematopoiesis is established by hundreds of precursors throughout mammalian ontogeny
Ganuza, M., Hall, T., Finkelstein, D., Chabot, A., Kang, G., & McKinney-Freeman, S. (2017) · Nature Cell Biology · doi:10.1038/ncb3607 · Cited by 94 · see citing works
Do haematopoietic stem cells age?
Dorshkind, K. A., Höfer, T., Montecino‐Rodriguez, E., Pioli, P. D., & Rodewald, H.-R. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0236-2 · Cited by 92 · see citing works
The many faces of hematopoietic stem cell heterogeneity
Crisan, M., & Dzierzak, E. A. (2016) · Development · doi:10.1242/dev.114231 · Cited by 89 · see citing works
Chen, Z., Amro, E. M., Becker, F. R., Hölzer, M., Rasa, S. M. M., Njeru, S. N., Han, B., Sanzo, S. D., Chen, Y.-L., Tang, D., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20181505 · Cited by 87 · see citing works
Pelissier, F. A., Garbe, J. C., Ananthanarayanan, B., Miyano, M., Lin, C., Jokela, T. A., Kumar, S., Stampfer, M. R., Lorens, J. B., & LaBarge, M. A. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.05.021 · Cited by 87 · see citing works
Clonal-level lineage commitment pathways of hematopoietic stem cells in vivo
Lu, R., Czechowicz, A. D., Seita, J., Du, J., & Weissman, I. L. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1801480116 · Cited by 85 · see citing works
Kent, D. G., Li, J., Tanna, H., Fink, J., Kirschner, K., Pask, D. C., Silber, Y., Hamilton, T. L., Sneade, R., Simons, B. D., et al. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001576 · Cited by 85 · see citing works
Stem cells: Aging and transcriptional fingerprints
Keyes, B. E., & Fuchs, E. V. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201708099 · Cited by 84 · see citing works
Hohman, L. S., & Osborne, L. C. (2022) · Aging Cell · doi:10.1111/acel.13700 · Cited by 83 · see citing works
Aging-Associated Changes in Hematopoiesis and Leukemogenesis: What's the Connection?
Henry, C. J., Marusyk, A., & DeGregori, J. V. (2011) · Aging · doi:10.18632/aging.100351 · Cited by 83 · see citing works
Brosh, R. M., Bellani, M. A., Liu, Y., & Seidman, M. M. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.05.005 · Cited by 81 · see citing works
Chen, J., Kelley, W. J., & Goldstein, D. R. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.2000380 · Cited by 80 · see citing works
Montecino‐Rodriguez, E., Kong, Y., Casero, D., Rouault, A., Dorshkind, K. A., & Pioli, P. D. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.01.016 · Cited by 79 · see citing works
Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches
Zhang, L., Mack, R. M., Breslin, P., & Zhang, J. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00994-z · Cited by 78 · see citing works
Molecular mechanisms underlying lineage bias in aging hematopoiesis
Elias, H. K., Bryder, D., & Park, C. Y. (2016) · Seminars in Hematology · doi:10.1053/j.seminhematol.2016.11.002 · Cited by 78 · see citing works
Causes and Mechanisms of Hematopoietic Stem Cell Aging
Lee, J., Yoon, S. R., Choi, I., & Jung, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061272 · Cited by 76 · see citing works
Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells
Quéré, R., Saint-Paul, L., Carmignac, V., Martin, R. Z., Chrétien, M., Largeot, A., Hammann, A., de Barros, J.-P. P., Bastie, J.-N., & Delva, L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405546111 · Cited by 71 · see citing works
Roeder, I., Horn, K., Sieburg, H. B., Cho, R. H., Müller‐Sieburg, C. E., & Loeffler, M. (2008) · Blood · doi:10.1182/blood-2008-05-155374 · Cited by 71 · see citing works
Self-citationGanuza, M., Hall, T., Finkelstein, D., Wang, Y., Chabot, A., Kang, G., Bi, W., Wu, G., & McKinney‐Freeman, S. (2019) · Blood · doi:10.1182/blood-2018-09-873059 · Cited by 71 · see citing works
Chavakis, T., Wielockx, B., & Hajishengallis, G. (2021) · Annual Review of Physiology · doi:10.1146/annurev-physiol-052521-013627 · Cited by 70 · see citing works
Effects of aging on hematopoietic stem and progenitor cells
Waterstrat, A., & Zant, G. E. V. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.05.002 · Cited by 70 · see citing works
Aging of the hematopoietic system
Snoeck, H. (2013) · Current Opinion in Hematology · doi:10.1097/moh.0b013e3283623c77 · Cited by 69 · see citing works
Meijers, R. W. J., Litjens, N. H. R., de Wit, E. A., Langerak, A. W., Baan, C. C., & Betjes, M. G. H. (2014) · Transplant International · doi:10.1111/tri.12416 · Cited by 65 · see citing works
Impact of Donor Age on Outcome after Allogeneic Hematopoietic Cell Transplantation
Rezvani, A. R., Storer, B. E., Guthrie, K. A., Schoch, H. G., Maloney, D. G., Sandmaier, B. M., & Storb, R. F. (2014) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2014.09.021 · Cited by 65 · see citing works
Geiger, H., Denkinger, M. D., & Schirmbeck, R. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.05.002 · Cited by 64 · see citing works
Immunosenescence and organ transplantation
Heinbokel, T., Elkhal, A., Liu, G., Edtinger, K., & Tullius, S. G. (2013) · Transplantation Reviews · doi:10.1016/j.trre.2013.03.001 · Cited by 63 · see citing works
Su, T., Hauenstein, J., Somuncular, E., Dumral, Ö., Leonard, E., Gustafsson, C., Tzortzis, E., Forlani, A., Johansson, A.-S., Qian, H., et al. (2023) · bioRxiv · doi:10.1038/s41467-024-52318-1 · Cited by 56 · see citing works
- Authors
- Cho, R. H., Sieburg, H. B., & Muller-Sieburg, C. E.
- Affiliations
- Sidney Kimmel Cancer Center (US)
- Sidney Kimmel Cancer Center, San Diego, CA
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2008-06-15
- Volume
- 111
- Issue
- 12
- Pages
- 5553-5561
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2424153
- OpenAlex
- W1974139477
- Cited by
- 377
- References
- 62
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 23 · 2023: 27 · 2022: 18 · 2021: 19 · 2020: 26 · 2019: 22 · 2018: 16 · 2017: 19 · 2016: 24 · 2015: 20 · 2014: 22 · 2013: 31 · 2012: 23
- FWCI
- 11.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Miami
- National Institutes of Health
- National Institute on Aging (R01AG023197, AG023197)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK048015, R01DK048015, R56DK048015)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- hematopoietic stem cells, aging, clonal composition, self-renewal, clonal analysis, T cell precursors, B cell precursors, genetic factors, C57BL/6 mice, immunosenescence
- MeSH terms
- Aging, Animals, B-Lymphocytes, Blood, Clone Cells, Genetic Markers, Hematopoietic Stem Cells, Lymphocytes, Mice, Inbred Strains, Mice, Transgenic, T-Lymphocytes, Thymus Gland, Cellular Senescence, Cell Lineage, Mice, Congenic, Myeloid Cells, Mice
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
