Cell intrinsic alterations underlie hematopoietic stem cell aging
Open accessAbstract
Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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 age-related rise in myeloid lineage gene expression likely comes from accumulation of myeloid-biased hematopoietic stem cells.
“The age-related increase in expression of myeloid lineage genes in the studies noted above (11,17) likely resulted from the accumulation of myeloid-biased HSCs, as these analyses were performed on unseparated pools of HSCs.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [11]
The shift toward myeloid potential in aged hematopoietic stem cells correlates with higher expression of myeloid lineage genes and lower expression of lymphoid lineage genes.
“This shift has been correlated with increased expression of myeloid lineage genes and downregulation of those specifying a lymphoid lineage fate (11,17).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [11]
The causes of age-related decline in lymphocyte development are multifactorial, involving changes in hematopoietic stem cells and progenitors as well as local tissue and systemic environments.
“The causes of this age-related reduction in lymphocyte development are multifactorial and include changes in HSCs and progenitor cells (11,12) as well as the local tissue and systemic environments (13,14).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [11]
The most profound immunologic effect of stem cell aging in mice and humans is a reduced ability to generate lymphocytes and an increased myeloid potential.
“From an immunologic perspective, the most profound effect of stem cell aging in both mice (11,18) and humans (17) is a decreased capacity to produce lymphocytes and an increase in myeloid potential.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [11]
Young bone marrow cells engraft less well in aged recipients than in young recipients.
“young bone marrow cells, when transplanted into aged recipients, engraft worse than when transplanted into young recipients.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [12]
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 Rossi et al., 2005
Cites
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206 · see citing works
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219 · see citing works
Stem cells, cancer, and cancer stem cells
Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001) · Nature · doi:10.1038/35102167 · Cited by 9,738 · see citing works
Self-citationModel-based analysis of oligonucleotide arrays: Expression index computation and outlier detection.
Li, C., & Wong, W. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.31 · Cited by 3,133 · see citing works
Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.
Goodell, M. A., Brose, K., Paradis, G. A., Conner, A. N., & Mulligan, R. C. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.4.1797 · Cited by 2,902 · see citing works
Purification and Characterization of Mouse Hematopoietic Stem Cells
Spangrude, G. J., Heimfeld, S., & Weissman, I. L. (1988) · Science · doi:10.1126/science.2898810 · Cited by 2,889 · see citing works
Self-citationA clonogenic common myeloid progenitor that gives rise to all myeloid lineages
Akashi, K., Traver, D., Miyamoto, T., & Weissman, I. L. (2000) · Nature · doi:10.1038/35004599 · Cited by 2,617 · see citing works
Self-citationIdentification of Clonogenic Common Lymphoid Progenitors in Mouse Bone Marrow
Kondo, M., Weissman, I. L., & Akashi, K. (1997) · Cell · doi:10.1016/s0092-8674(00)80453-5 · Cited by 2,253 · see citing works
Self-citationLong-Term Lymphohematopoietic Reconstitution by a Single CD34-Low/Negative Hematopoietic Stem Cell
Osawa, M., Hanada, K., Hamada, H., & Nakauchi, H. (1996) · Science · doi:10.1126/science.273.5272.242 · Cited by 2,141 · see citing works
Gene regulation and DNA damage in the ageing human brain
Lu, T., Pan, Y., Kao, S.-Y., Li, C., Kohane, I., Chan, J., & Yankner, B. A. (2004) · Nature · doi:10.1038/nature02661 · Cited by 1,874 · see citing works
Gene expression profile of aging and its retardation by caloric restriction
Lee, C.-K., Klopp, R. G., Weindruch, R., & Prolla, T. A. (1999) · Science · doi:10.1126/science.285.5432.1390 · Cited by 1,473 · see citing works
GOstat: find statistically overrepresented Gene Ontologies within a group of genes
Beißbarth, T., & Speed, T. P. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth088 · Cited by 1,256 · see citing works
Identification of Flt3+ Lympho-Myeloid Stem Cells Lacking Erythro-Megakaryocytic Potential
Adolfsson, J., Månsson, R., Buza-Vidas, N., Hultquist, A., Liuba, K., Jensen, C. T., Bryder, D., Yang, L., Borge, O. J., Thorén, L., et al. (2005) · Cell · doi:10.1016/j.cell.2005.02.013 · Cited by 1,229 · see citing works
Self-citationAge-related changes in lymphocyte development and function
Linton, P. J., & Dorshkind, K. A. (2004) · Nature Immunology · doi:10.1038/ni1033 · Cited by 1,180 · see citing works
Gene-expression profile of the ageing brain in mice
Lee, C.-K., Weindruch, R., & Prolla, T. A. (2000) · Nature Genetics · doi:10.1038/77046 · Cited by 1,055 · see citing works
Biology of Hematopoietic Stem Cells and Progenitors: Implications for Clinical Application
Kondo, M., Wagers, A. J., Manz, M. G., Prohaska, S. S., Scherer, D. C., Beilhack, G. F., Shizuru, J. A., & Weissman, I. L. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141007 · Cited by 992 · see citing works
Self-citationCheshier, S. H., Morrison, S. J., Liao, X., & Weissman, I. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3120 · Cited by 858 · 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
Self-citationChristensen, J. L., & Weissman, I. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261562798 · Cited by 786 · see citing works
Self-citationAssociation of Spindle Assembly Checkpoint Component XMAD2 with Unattached Kinetochores
Chen, R., Waters, J. C., Salmon, E. D., & Murray, A. W. (1996) · Science · doi:10.1126/science.274.5285.242 · Cited by 783 · 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
Multilineage gene expression precedes commitment in the hemopoietic system.Preprint
Hu, M., Krause, D. S., Greaves, M. F., Sharkis, S. J., Dexter, M., Heyworth, C. M., & Enver, T. (1997) · Genes & Development · doi:10.1101/gad.11.6.774 · Cited by 719 · see citing works
Adolfsson, J., Borge, O. J., Bryder, D., Theilgaard‐Mönch, K., Åstrand‐Grundström, I., Sitnicka, E., Sasaki, Y., & Jacobsen, S. E. W. (2001) · Immunity · doi:10.1016/s1074-7613(01)00220-5 · Cited by 712 · see citing works
Self-citationIkuta, K., & Weissman, I. L. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.4.1502 · Cited by 637 · see citing works
Self-citationClass-switch recombination: interplay of transcription, DNA deamination and DNA repair
Chaudhuri, J., & Alt, F. W. (2004) · Nature reviews. Immunology · doi:10.1038/nri1395 · Cited by 623 · see citing works
Ikuta, K., Kina, T., MacNeil, I., Uchida, N., Peault, B., Chien, Y.-H., & Weissman, I. L. (1990) · Cell · doi:10.1016/0092-8674(90)90262-d · Cited by 583 · see citing works
Self-citationYang, L., Bryder, D., Adolfsson, J., Nygren, J., Månsson, R., Sigvardsson, M., & Jacobsen, S. E. W. (2004) · Blood · doi:10.1182/blood-2004-06-2159 · Cited by 469 · see citing works
Self-citationMcCarroll, S. A., Murphy, C. T., Zou, S., Pletcher, S. D., Chin, C.-S., Jan, Y. N., Kenyon, C., Bargmann, C. I., & Li, H. (2004) · Nature Genetics · doi:10.1038/ng1291 · Cited by 454 · see citing works
Myeloid or Lymphoid Promiscuity as a Critical Step in Hematopoietic Lineage Commitment
Miyamoto, T., Iwasaki, H., Reizis, B., Ye, M., Graf, T., Weissman, I. L., & Akashi, K. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00201-0 · Cited by 415 · see citing works
Self-citationThe Genetic Program of Hematopoietic Stem Cells
Phillips, R. L., Ernst, R., Brunk, B. P., Ivanova, N. B., Mahan, M. A., Deanehan, J. K., Moore, K. A., Overton, G. C., & Lemischka, I. R. (2000) · Science · doi:10.1126/science.288.5471.1635 · Cited by 411 · see citing works
Kayo, T., Allison, D. B., Weindruch, R., & Prolla, T. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081061898 · Cited by 384 · see citing works
Akashi, K., He, X., Chen, J., Iwasaki, H., Niu, C. S., Steenhard, B. M., Zhang, J., Haug, J., & Li, L. (2002) · Blood · doi:10.1182/blood-2002-06-1780 · Cited by 368 · see citing works
Competitive 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
de Haan, G., NIJHOF, W., & Zant, G. E. V. (1997) · Blood · doi:10.1182/blood.v89.5.1543 · Cited by 300 · see citing works
Unexpectedly Efficient Homing Capacity of Purified Murine Hematopoietic Stem Cells
Matsuzaki, Y., Kinjo, K., Mulligan, R. C., & Okano, H. (2004) · Immunity · doi:10.1016/s1074-7613(03)00354-6 · Cited by 290 · 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
Concepts of human leukemic development
Warner, J. K., Wang, J. C. Y., Hope, K. J., Jin, L., & Dick, J. E. (2004) · Oncogene · doi:10.1038/sj.onc.1207933 · Cited by 222 · see citing works
THE FATE OF SERIALLY TRANSPLANTED BONE MARROW CELL POPULATIONS FROM YOUNG AND OLD DONORS
Ogden, D. A., & Micklem, H. S. (1976) · Transplantation · doi:10.1097/00007890-197609000-00010 · Cited by 146 · 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
Micklem, H. S., Ford, C. E., Evans, E. P., Ogden, D. A., & Papworth, D. G. (1972) · Journal of Cellular Physiology · doi:10.1002/jcp.1040790214 · Cited by 102 · see citing works
Albright, J. W., & Makinodan, T. (1976) · The Journal of Experimental Medicine · doi:10.1084/jem.144.5.1204 · Cited by 95 · see citing works
Does functional depletion of stem cells drive aging?
Schlessinger, D., & Zant, G. E. V. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00299-8 · Cited by 62 · see citing works
Normal Function of Immunologic Stem Cells from Aged Mice
Harrison, D. E., & Doubleday, J. W. (1975) · The Journal of Immunology · doi:10.4049/jimmunol.114.4.1314 · Cited by 60 · see citing works
Hardy, R. R., Wei, C., & Hayakawa, K. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.0100.x · Cited by 59 · 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
Genetic control of stem-cell properties and stem cells in aging
Liang, Y., & Zant, G. E. V. (2003) · Current Opinion in Hematology · doi:10.1097/00062752-200305000-00001 · Cited by 28 · see citing works
Flagged first, then by citations
1 of the 47 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Hematopoiesis: An Evolving Paradigm for Stem Cell Biology
Orkin, S. H., & Zon, L. I. (2008) · Cell · doi:10.1016/j.cell.2008.01.025 · Cited by 2,570 · see citing works
“Several changes in gene expression of old versus young HSCs have been described, including increased expression of leukemia-associated genes and decreased expression of genes contributing to DNA damage repair, genomic integrity, and chromatin remodeling (Rossi et al., 2005; Nijnik et al., 2007).”
BackgroundParacrine Mechanisms in Adult Stem Cell Signaling and Therapy
Gnecchi, M., Zhang, Z., Ni, A., & Dzau, V. J. (2008) · Circulation Research · doi:10.1161/circresaha.108.176826 · Cited by 2,030 · see citing works
Deficiencies 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
Self-citationAge-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
Oxidative Stress, Mitochondrial Dysfunction, and Aging
Cui, H., Kong, Y., & Zhang, H. (2011) · Journal of Signal Transduction · doi:10.1155/2012/646354 · Cited by 1,036 · see citing works
“Particularly, mitochondria are thought to play an important role in the pathogenesis of age-associated neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease.”
BackgroundHuman 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
“Notably, the results from our functional analysis and gene expression profiling of young and elderly human HSC significantly parallel the data we and others have generated on young and elderly mouse HSC (2, 6, 36).”
BackgroundResultSelf-citationHaematopoietic 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
Bearzi, C., Rota, M., Hosoda, T., Tillmanns, J., Nascimbene, A., Angelis, A. D., Yasuzawa-Amano, S., Trofimova, I., Siggins, R. W., LeCapitaine, N. J., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706760104 · Cited by 978 · see citing works
Hematopoietic stem cell: self‐renewal versus differentiation
Seita, J., & Weissman, I. L. (2010) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.86 · Cited by 925 · see citing works
Self-citationStems Cells and the Pathways to Aging and Cancer
Rossi, D. J., Jamieson, C. H. M., & Weissman, I. L. (2008) · Cell · doi:10.1016/j.cell.2008.01.036 · Cited by 895 · see citing works
“Intriguingly, Bmi-1-mediated suppression of the p16Ink4a-p19Arf locus is dependent upon the presence of Ezh2 (Bracken et al., 2007), suggesting a mechanism through which reduced expression of Ezh2 in aged HSCs (Rossi et al., 2005) may lead to induction of p16Ink4a (Janzen et al., 2006).”
BackgroundInfluentialSelf-citationImmunosenescence: emerging challenges for an ageing population
Aw, D., Silva, A. B., & Palmer, D. B. (2007) · Immunology · doi:10.1111/j.1365-2567.2007.02555.x · Cited by 880 · see citing works
Kowalczyk, M. S., Tirosh, I., Heckl, D., Rao, T. N., Dixit, A., Haas, B. J., Schneider, R. K., Wagers, A. J., Ebert, B. L., & Regev, A. (2015) · Genome Research · doi:10.1101/gr.192237.115 · Cited by 778 · see citing works
“S4C; as defined by Sanjuan-Pla et al. 2013), such that old cells express, on average, higher levels of MkP signature genes than their young counterparts, and lessdifferentiated cells have higher MkP expression levels than more differentiated cells (P < 10−6 for all pairwise comparisons by…”
BackgroundMethodSelf-citationDNA Methylation in Cancer and Aging
Klutstein, M., Nejman, D., Greenfield, R., & Cedar, H. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-3278 · Cited by 810 · see citing works
“Interestingly, several studies have already established that hematopoietic stem cells from bothmouse andman actually undergo a natural aging process whereby they increase in number while their lymphoid differentiation capacity is diminished, leading to a myeloid-dominant phenotype (34).”
BackgroundFoxo3a is essential for maintenance of the hematopoietic stem cell pool
Miyamoto, K., Kazuhito, N., & Atsushi, H. (2009) · Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) · Cited by 858 · see citing works
How stem cells age and why this makes us grow old
Sharpless, N. E., & DePinho, R. A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2241 · Cited by 843 · see citing works
“Additionally, as stem cells appear to be less metabolically active in their quiescent state, they may be subjected to lower levels of DNA-damage-inducing metabolic side products such as reactive oxygen species (ROS”
BackgroundAging 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
“Many of the observed expression changes are corroborated by a recent study of HSC aging [4].”
BackgroundResultInfluentialNo place like home: anatomy and function of the stem cell niche
Jones, D. L., & Wagers, A. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2319 · Cited by 794 · see citing works
“In some cases, cell autonomous changes have been proposed to have a role in observed decreases in tissue stem cell functio”
BackgroundSelf-citationCauses, 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
“This shift has been correlated with increased expression of myeloid lineage genes and downregulation of those specifying a lymphoid lineage fate (11, 17).”
InfluentialHematopoietic stem cell niche maintenance during homeostasis and regeneration
Mendelson, A., & Frenette, P. S. (2014) · Nature Medicine · doi:10.1038/nm.3647 · Cited by 783 · see citing works
Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domainsPreprint
Rakyan, V. K., Down, T. A., Maslau, S., Andrew, T., Yang, T.-P., Beyan, H., Whittaker, P., McCann, O. T., Finer, S., Valdes, A. M., et al. (2010) · Genome Research · doi:10.1101/gr.103101.109 · Cited by 750 · see citing works
Bryder, D., Rossi, D. J., & Weissman, I. L. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.060312 · Cited by 733 · see citing works
Self-citationSun, 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
“…have established that, with age, phenotypically defined mouse and human HSCs increase in number, whereas lymphoid cell production is diminished, leading to a myeloid-dominant hematopoietic system (Chambers et al., 2007b; de Haan and Van Zant, 1999; Morrison et al., 1996; Rossi et al., 2005).”
BackgroundBeerman, 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
“This age-associated lineage bias has been shown to result from age-dependent differences in the propensity of HSCs from young or old mice to commit and give rise to primitive oligo-potent myeloid or lymphoid progenitors (11, 14).”
BackgroundMethodResultInfluentialSelf-citationStem cells, ageing and the quest for immortality
Rando, T. A. (2006) · Nature · doi:10.1038/nature04958 · Cited by 695 · see citing works
“Recently, direct molecular analysis of purified HS cells revealed differences in gene expression between cells from young and old mic”
BackgroundmTOR 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
“Consistent with previous studies, hematopoietic reconstitution by HSCs from old mice was decreased compared to that by HSCs from young mice (1, 20).”
Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells
Flach, J., Bakker, S. T., Mohrin, M., Conroy, P. C., Pietras, E. M., Reynaud, D., Alvarez, S., Diolaiti, M. E., Ugarte, F., Forsberg, E. C., et al. (2014) · Nature · doi:10.1038/nature13619 · Cited by 650 · 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
“Several studies suggest that cells with a differentiation characteristics may increase as mice age (Sudo et al., 2000; Kim et al., 2003; Rossi et al., 2005; Liang et al., 2005).”
BackgroundThe ageing haematopoietic stem cell compartment
Geiger, H., de Haan, G., & Florian, M. C. (2013) · Nature Reviews Immunology · doi:10.1038/nri3433 · Cited by 604 · see citing works
Mechanisms of Stem Cell Self-Renewal
He, S., Nakada, D., & Morrison, S. J. (2009) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.042308.113248 · Cited by 607 · see citing works
“Aging HSCs also exhibit increased myelopoiesis and decreased lymphopoiesis (Rossi et al. 2005) as well as decreased capacity to home to the bone marrow upon intravenous injection (Liang et al. 2005, Morrison et al. 1996b).”
BackgroundCdc42 activity regulates hematopoietic stem cell aging and rejuvenation
Florian, M. C., Dörr, K., Niebel, A., Daria, D., Schrezenmeier, H., Rojewski, M., Filippi, M.-D., Hasenberg, A., Gunzer, M., Scharffetter-Kochanek, K., et al. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.04.007 · Cited by 564 · see citing works
“…and Goodell, 2007; Dorshkind and Swain, 2009; Geiger et al., 2005; Geiger and Van Zant, 2002; Ju et al., 2007; Morrison et al., 1996; Rando, 2006; Rossi et al., 2005) and manifests as decreased immune response (Linton and Dorshkind, 2004), increased myelogenous disease (Kiss et al., 2007; Signer…”
InfluentialJNK Activity in Somatic Stem Cells Causes Loss of Tissue Homeostasis in the Aging Drosophila Gut
Biteau, B., Hochmuth, C. E., & Jasper, H. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.07.024 · Cited by 583 · see citing works
“Holbrook, 2000; Rossi et al., 2005; Tothova et al., 2007).”
BackgroundDistinct 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
“Our lab and others have shown that aging mouse HSCs show a decline in long-term reconstituting potential (Chambers et al., 2007; Rossi et al., 2007) and a deficit in lymphopoiesis (Sudo et al., 2000; Rossi et al., 2005).”
InfluentialAnemia in Clinical Practice—Definition and Classification: Does Hemoglobin Change With Aging?
Cappellini, M. D., & Motta, I. (2015) · Seminars in Hematology · doi:10.1053/j.seminhematol.2015.07.006 · Cited by 564 · see citing works
Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis
McKerrell, T., Park, N., Moreno, T., Grove, C. S., Ponstingl, H., Stephens, J., Crawley, C., Craig, J., Scott, M. A., Hodkinson, C., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.02.005 · Cited by 534 · see citing works
“…changes in cell-intrinsic properties of HSCs in both mice (Cham- 1242 Cell Reports 10, 1239–1245, March 3, 2015 ª2015 The Authors bers et al., 2007; Rossi et al., 2005) and humans (Rübe et al., 2011; Taraldsrud et al., 2009), and it is also clear that aging has a profound effect on the…”
BackgroundClonal 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
“…of these differences is that upon transplantation; old HSCs tend to have a myeloid-skewed blood cell production caused by a decreased ability to produce lymphoid cells (Sudo et al., 2000; Kim et al., 2003; Liang et al., 2005; Rossi et al., 2005; Cho et al., 2008; Beerman et al., 2010a).”
BackgroundDNA 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
Beerman, I., Bock, C., Garrison, B. S., Smith, Z. D., Gu, H., Meissner, A., & Rossi, D. J. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.01.017 · Cited by 485 · see citing works
“…chromosomal regions (Chambers et al., 2007) and of gene sets involved in myeloid and lymphoid lineage commitment in HSCs purified from old mice and humans (Chambers et al., 2007; Pang et al., 2011; Rossi et al., 2005), which suggests a mechanism involving coordinated genome-wide regulatory control.”
InfluentialSelf-citationAging and Replicative Senescence Have Related Effects on Human Stem and Progenitor Cells
Wagner, W., Bork, S., Horn, P., Krunic, D., Walenda, T., Diehlmann, A., Beneš, V., Blake, J., Huber, F.-X., Eckstein, V., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005846 · Cited by 480 · see citing works
“Rossi and co-workers analyzed differential expression of HPC (c-kit, lineage, Sca-1, flk2(2), CD34(2)) from young (2–3 month) and old (22–24 month) mice by microarray [34].”
BackgroundAging 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
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
“…contribute to many of these age-related phenotypes through diverse mechanisms involving diminution of regenerative potential (Dykstra et al., 2011; Rossi et al., 2005; Sudo et al., 2000), changes in lineage potential and HSC subtype composition (Beerman et al., 2010; Challen et al., 2010; Dykstra…”
BackgroundResultInfluentialSelf-citationEfficient Transplantation via Antibody-Based Clearance of Hematopoietic Stem Cell Niches
Czechowicz, A. D., Kraft, D. L., Weissman, I. L., & Bhattacharya, D. (2007) · Science · doi:10.1126/science.1149726 · Cited by 432 · see citing works
Self-citationAgeing and atherosclerosis: vascular intrinsic and extrinsic factors and potential role of IL-6
Tyrrell, D. J., & Goldstein, D. R. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-0431-7 · Cited by 434 · see citing works
Sato, T., Onai, N., Yoshihara, H., Arai, F., Suda, T., & Ohteki, T. (2009) · Nature Medicine · doi:10.1038/nm.1973 · Cited by 412 · see citing works
The ageing immune system: is it ever too old to become young again?
Dorshkind, K. A., Montecino‐Rodriguez, E., & Signer, R. A. J. (2008) · Nature reviews. Immunology · doi:10.1038/nri2471 · Cited by 412 · 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
“…performed, they do not uncover any particular changes in cell cycle machinery or upstream regulatory genes in old HSCs, though alterations in the expression of genes involved in myeloid and lymphoid differentiation and epigenetic regulation are observed (Rossi et al., 2005; Chambers et al., 2007).”
BackgroundAgeing and rejuvenation of tissue stem cells and their niches
Brunet, A., Goodell, M. A., & Rando, T. A. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00510-w · Cited by 407 · 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 the immune system: An overview
Akha, A. A. S. (2018) · Journal of Immunological Methods · doi:10.1016/j.jim.2018.08.005 · Cited by 389 · see citing works
Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche
Maryanovich, M., Zahalka, A. H., Pierce, H., Pinho, S., Nakahara, F., Asada, N., Wei, Q., Wang, X., Ciero, P., Xu, J., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0030-x · Cited by 389 · see citing works
“Further evaluation of lineage-selective gene sets, focusing on those reported to be differentially expressed in old HSCs 11 , revealed a restoration toward levels in yHSCs, with more profound effects observed for the lymphoid-lineage genes (Fig.”
Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function
Garaycoechea, J. I., Crossan, G. P., Langevin, F., Daly, M. G., Arends, M. J., & Patel, K. J. (2012) · Nature · doi:10.1038/nature11368 · Cited by 382 · see citing works
Immune ageing at single-cell resolution
Mogilenko, D. A., Shchukina, I., & Artyomov, M. N. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00646-4 · Cited by 392 · see citing works
Life and Death of Cardiac Stem Cells
Anversa, P., Kajstura, J., Leri, A., & Bolli, R. (2006) · Circulation · doi:10.1161/circulationaha.105.595181 · Cited by 385 · see citing works
Aged skeletal stem cells generate an inflammatory degenerative niche
Ambrosi, T. H., Marecic, O., McArdle, A., Sinha, R., Gulati, G. S., Tong, X., Wang, Y., Steininger, H. M., Hoover, M. Y., Koepke, L. S., et al. (2021) · Nature · doi:10.1038/s41586-021-03795-7 · Cited by 392 · see citing works
Self-citationCho, R. H., Sieburg, H. B., & Muller-Sieburg, C. E. (2008) · Blood · doi:10.1182/blood-2007-11-123547 · Cited by 377 · 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…”
BackgroundOxidative Stress in the Regulation of Normal and Neoplastic Hematopoiesis
Ghaffari, S. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2142 · Cited by 377 · see citing works
“The replicative capacity and function of hematopoietic stem cells is reduced with age (21, 22, 98).”
The polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion
Kamminga, L. M., Bystrykh, L. V., de Boer, A., Houwer, S., Douma, J., Weersing, E., Dontje, B., & de Haan, G. (2006) · Blood · doi:10.1182/blood-2005-09-3585 · Cited by 376 · 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
“, upregulated stress responses, increased proinflammatory signaling, protein misfolding, downregulated DNA repair machinery, and aberrant chromatin modification (19, 33, 37).”
BackgroundInfluentialDay, K. R., Waite, L. L., Thalacker‐Mercer, A. E., West, A. B., Bamman, M. M., Brooks, J. D., Myers, R., & Absher, D. (2013) · Genome biology · doi:10.1186/gb-2013-14-9-r102 · Cited by 363 · see citing works
“Transplanted hematopoietic stem cells from old mice also demonstrated a bias toward the myeloid lineage [50].”
BackgroundAn Epigenetic Signature in Peripheral Blood Predicts Active Ovarian Cancer
Teschendorff, A. E., Menon, U., Gentry‐Maharaj, A., Ramus, S. J., Gayther, S. A., Apostolidou, S., Jones, A., Lechner, M., Beck, S., Jacobs, I. J., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008274 · Cited by 357 · see citing works
“lymphocyte ratio [25–29], a pattern consistent with our observation that granulocyte and T-lymphocyte specific genes were enriched”
BackgroundLifespan Extension by Preserving Proliferative Homeostasis in Drosophila
Biteau, B., Karpac, J., Supoyo, S., DeGennaro, M., Lehmann, R., & Jasper, H. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001159 · Cited by 346 · 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
“Specifically, the LT-HSC population (LSKCD342Flt32 or LSKCD482CD1501) accumulated with age, whereas the LSKCD341Flt31 population (containing lymphoid-primed multipotent progenitors [LMPPs]) decreased (supplemental Figure 1A), as previously described.(1) In young mice (aged 2 months), CD41 expression on LSKs was low (;…”
ResultGrover, 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
Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians
Hashimoto, K., Kouno, T., Ikawa, T., Hayatsu, N., Miyajima, Y., Yabukami, H., Terooatea, T., Sasaki, T., Suzuki, T., Valentine, M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1907883116 · Cited by 343 · see citing works
“5 stem cells in bone marrow exhibit a myeloid-biased differentiation potential (12, 13), which 70 causes changes in the cell population of peripheral blood.”
BackgroundA 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
Dynamic niches in the origination and differentiation of haematopoietic stem cells
Wang, L. D., & Wagers, A. J. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3184 · Cited by 343 · see citing works
Self-citationp53-Mediated Hematopoietic Stem and Progenitor Cell Competition
Bondar, T., & Medzhitov, R. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.03.002 · Cited by 342 · see citing works
“In addition, P-selectin and Sdpr, which are upregulated in aged HSCs (Chambers et al., 2007; Rossi et al., 2005), were also upregulated in loser and downregulated in winner HSPC cells (Figure 6B).”
Neutrophil phenotypes and functions in cancer: A consensus statement
Quail, D. F., Amulic, B., Aziz, M., Barnes, B. J., Eruslanov, E. B., Fridlender, Z. G., Goodridge, H. S., Granot, Z., Hidalgo, A., Huttenlocher, A., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20220011 · Cited by 336 · 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
“The cause of lineage skewing is unknown, but could involve stable epigenetic changes (60, 61).”
BackgroundBenz, 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
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
“experiments, old HSCs transferred to young hosts retain their aged phenotype (Rossi et al., 2005), supporting the notion that HSC aging is largely driven by cell-intrinsic mechanisms.”
BackgroundT Cell Replicative Senescence in Human Aging
P. Chou, J., & B. Effros, R. (2013) · Current Pharmaceutical Design · doi:10.2174/138161213805219711 · Cited by 323 · see citing works
A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing
Florian, M. C., Nattamai, K. J., Dörr, K., Marka, G., Überle, B., Vas, V., Eckl, C., Andrä, I., Schiemann, M., Oostendorp, R. A. J., et al. (2013) · Nature · doi:10.1038/nature12631 · Cited by 303 · see citing works
Ho, Y.-H., del Toro, R., Rivera-Torres, J., Rak, J., Korn, C., García-García, A., Macías, D., González-Gómez, C., del Monte, A., Wittner, M., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.06.007 · Cited by 315 · see citing works
“Hematopoietic aging is characterized by expansion of hematopoietic stem cells (HSCs) with impaired function, such as reduced engraftment, quiescence, self-renewal, unfolded protein response, and lymphoid differentiation potential, leading to myeloid-biased output both in mice (Liang et al., 2005; Mohrin et al., 2015;…”
BackgroundTNF-α–driven inflammation and mitochondrial dysfunction define the platelet hyperreactivity of aging
Davizon‐Castillo, P., McMahon, B. J., Águila, S., Bark, D. L., Ashworth, K. J., Allawzi, A. M., Campbell, R. A., Montenont, E., Nemkov, T. G., D’Alessandro, A., et al. (2019) · Blood · doi:10.1182/blood.2019000200 · Cited by 317 · see citing works
Age-associated epigenetic drift: implications, and a case of epigenetic thrift?
Teschendorff, A. E., West, J., & Beck, S. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt375 · Cited by 318 · see citing works
The chronic myeloid leukemia stem cell: stemming the tide of persistence
Holyoake, T. L., & Vetrie, D. L. P. (2017) · Blood · doi:10.1182/blood-2016-09-696013 · Cited by 312 · see citing works
“and the detection of BCR-ABL1 in blood cells of normal individuals(26,27) present the possibility that heterogeneity could also be driven by mutations acquired before or after BCR-ABL1, or other factors such as deregulation and skewing of lineage specification, clonal hemopoiesis, DNA damage, activation of inflammator…”
BackgroundCell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells
Viale, A., Franco, F., Orleth, A., Cambiaghi, V., Giuliani, V., Bossi, D., Ronchini, C., Ronzoni, S., Muradore, I., Monestiroli, S., et al. (2008) · Nature · doi:10.1038/nature07618 · Cited by 303 · see citing works
Interconnections between Inflammageing and Immunosenescence during Ageing
Teissier, T., Boulanger, É., & Cox, L. S. (2022) · Cells · doi:10.3390/cells11030359 · Cited by 310 · see citing works
“Age-related accumulation of senescent cells in the bone marrow (including mesenchymal stem cells as well as bone macrophages and long-lived osteocytes) may contribute, through the SASP, to a pro-inflammatory microenvironment which favours differentiation of HSCs towards myeloid progenitors [169] at the expense of lymp…”
BackgroundManifestations 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
“Hematopoietic stem cells (HSCs) from both old humans and old mice show an increased propensity to differentiate along the myeloid rather than the lymphoid lineage (Sudo et al., 2000; Rossi et al., 2005).”
Macrophage Related Chronic Inflammation in Non-Healing Wounds
Li, M., Hou, Q., Zhong, L., Zhao, Y., & Fu, X. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.681710 · Cited by 299 · see citing works
“The comparative analysis of expression profiles of HSPCs suggested that the myeloid differentiation related genes in aged mice, such as Runx1, Hoxb6, andOsmr are upregulated while lymphopoiesis genes are downregulated compared with those of young mice (88).”
Changes in primary lymphoid organs with aging
Chinn, I. K., Blackburn, C. C., Manley, N. R., & Sempowski, G. D. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.005 · Cited by 282 · see citing works
“Myeloid skewing has been validated using microarray analyses, which show upregulation of myeloid genes and downregulation of lymphoid genes in bone marrow HSCs taken from 22 – 24 month-old mice compared to genes expressed in younger bone marrow HSCs at 2 – 3 months of age [3].”
MethodThe role of mitochondria in stem cell fate and aging
Zhang, H., Menzies, K. J., & Auwerx, J. H. (2018) · Development · doi:10.1242/dev.143420 · Cited by 285 · see citing works
“, 1996) and altered cell fate decisions (Rossi et al., 2005; Sudo et al., 2000).”
BackgroundHematopoietic 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
“…demonstrate reduced self-renewal (Dykstra et al., 2011), impaired homing and engraftment upon transplantation (Dykstra et al., 2011; Morrison et al., 1996), and myeloidbiased differentiation (Benz et al., 2012; Cho et al., 2008; Muller-Sieburg et al., 2004; Rossi et al., 2005; Sudo et al., 2000).”
Rantes/Ccl5 influences hematopoietic stem cell subtypes and causes myeloid skewing
Ergen, A. V., Boles, N. C., & Goodell, M. A. (2012) · Blood · doi:10.1182/blood-2011-11-391730 · Cited by 280 · see citing works
Unravelling stem cell dynamics by lineage tracing
Blanpain, C., & Simons, B. D. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3625 · Cited by 273 · see citing works
The stem cell niche in regenerative medicine.
Wagers, A. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.02.018 · Cited by 281 · see citing works
“In the blood system, HSC numbers increase with age but HSC function declines (Morrison et al., 1996; Rossi et al., 2005), leading to impaired stem cell engraftment potential and skewed production of mature cell lineages by individual aged HSCs (Dykstra et al., 2011).”
BackgroundSelf-citationSelf-renewal and differentiation capacity of young and aged stem cells
Roobrouck, V. D., Ulloa‐Montoya, F., & Verfaillie, C. M. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.03.006 · Cited by 267 · see citing works
Gene Expression Commons: An Open Platform for Absolute Gene Expression Profiling
Seita, J., Sahoo, D., Rossi, D. J., Bhattacharya, D., Serwold, T. F., Inlay, M. A., Ehrlich, L. I. R., Fathman, J. W., Dill, D. L., & Weissman, I. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040321 · Cited by 261 · see citing works
“0 CD342 Flk22 KLS (young) CD342 Flk22 KLS (old) 45000 34000 [26]”
Self-citationNorddahl, G. L., Pronk, C. J., Wahlestedt, M., Sten, G., Nygren, J. M., Ugale, A., Sigvardsson, M., & Bryder, D. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2011.03.009 · Cited by 249 · see citing works
“The HSC compartment undergoes a range of functional and phenotypic alterations with age (Rossi et al., 2005).”
BackgroundResultInfluentialSelf-citationRegulation of adult stem cell quiescence and its functions in the maintenance of tissue integrity
de Morrée, A., & Rando, T. A. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00568-6 · Cited by 243 · see citing works
Pbx1 Regulates Self-Renewal of Long-Term Hematopoietic Stem Cells by Maintaining Their Quiescence
Ficara, F., Murphy, M., Lin, M., & Cleary, M. L. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.03.004 · Cited by 235 · see citing works
“ROSSI_AGING_UP 0.00 Upregulated in LT-HSCs from aging mice (= higher self-renewal) ( Rossi et al., 2005 )”
BackgroundInfluentialThe hematopoietic stem cell niche: from embryo to adult
Gao, X., Xu, C., Asada, N., & Frenette, P. S. (2018) · Development · doi:10.1242/dev.139691 · Cited by 247 · see citing works
“Aged HSCs are more proliferative and their numbers increase in the aged bone marrow (de Haan et al., 1997; Dykstra et al., 2011; Morrison et al., 1996; Rossi et al., 2005).”
BackgroundIBD across the age spectrum—is it the same disease?
Ruel, J., Ruane, D., Mehandru, S., Gower‐Rousseau, C., & Colombel, J. (2013) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.240 · Cited by 237 · 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
“Aged murine haematopoietic stem cells (HSCs) exhibit a skewed differentiation potential toward the myeloid lineag”
BackgroundDepleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity
Ross, J., Myers, L. M., Noh, J. J., Collins, M. M., Carmody, A., Messer, R. J., Dhuey, E., Hasenkrug, K. J., & Weissman, I. L. (2024) · Nature · doi:10.1038/s41586-024-07238-x · Cited by 241 · see citing works
Self-citationInsights into Mesenchymal Stem Cell Aging: Involvement of Antioxidant Defense and Actin Cytoskeleton
Kasper, G., Mao, L., Geißler, S., Draycheva, A., Trippens, J., Kühnisch, J., Tschirschmann, M., Kaspar, K., Perka, C., Duda, G. N., et al. (2009) · Stem Cells · doi:10.1002/stem.49 · Cited by 230 · see citing works
Köhler, A., Schmithorst, V. J., Filippi, M., Ryan, M. A., Daria, D., Gunzer, M., & Geiger, H. (2009) · Blood · doi:10.1182/blood-2008-12-195644 · Cited by 225 · see citing works
Targeting immune dysfunction in aging
Borgoni, S., Kudryashova, K. S., Burka, K., & de Magalhães, J. P. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101410 · Cited by 227 · see citing works
“Indeed, in younger mice HSCs perform much better compared to older mice HSCs after transplantation, indicating higher potency (Dykstra et al., 2011; Rossi et al., 2005; Verovskaya et al., 2013).”
T cell regeneration after immunological injury
Velardi, E., Tsai, J. J., & van den Brink, M. R. M. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-00457-z · Cited by 222 · see citing works
Adelman, E. R., Huang, H.-T., Roisman, A., Olsson, A., Colaprico, A., Qin, T., Lindsley, R. C., Bejar, R. L., Salomonis, N., Grimes, H. L., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1474 · Cited by 222 · see citing works
- Authors
- Rossi, D. J., Bryder, D., Zahn, J. M., Ahlenius, H., Sonu, R., Wagers, A. J., & Weissman, I. L.
- Affiliations
- Joslin Diabetes Center (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-06-20
- Volume
- 102
- Issue
- 26
- Pages
- 9194-9199
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1153718
- OpenAlex
- W2131263031
- Cited by
- 1,152
- References
- 47
- Citations by year
- 2026: 44 · 2025: 56 · 2024: 49 · 2023: 55 · 2022: 56 · 2021: 80 · 2020: 57 · 2019: 71 · 2018: 57 · 2017: 59 · 2016: 67 · 2015: 54 · 2014: 56 · 2013: 63 · 2012: 55
- FWCI
- 24.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Damon Runyon Cancer Research Foundation
- National Institutes of Health
- Medical Research Council
- National Cancer Institute (R01CA086065)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- hematopoietic stem cell aging, long-term hematopoietic stem cells, stem cell self-renewal, leukemic transformation, age-related immune decline, gene expression profiling
- MeSH terms
- Animals, Cell Separation, Cell Transformation, Neoplastic, Flow Cytometry, Gene Expression Regulation, Hematopoiesis, Hematopoietic Stem Cells, Leukemia, Mice, Inbred C57BL, Software, Stem Cells, Down-Regulation, Up-Regulation, Genome, Cellular Senescence, Cell Transplantation, Cell Lineage, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, 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
