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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.
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“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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
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“To extend our findings to a more physiological system, we assayed the effect of SIRT1 deficiency on the establishment of the primitive HSC compartment, by quantitating the total number of HSCs and multipotent progenitors in BM from young (3–9 wk) Sirt1 knockout (Sirt11 / ) and control mice by flow cytometry using rigo…”
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“For instance, the key epigenetic regulator Ezh2 is down-regulated in aged HSCs.36 Although we previously found little evidence of epigenetic changes at the p16INK4a locus in aged HSCs,36 a wellestablished Ezh2 target loci in other cells,37 the broad and potent roles of Ezh2 might well underlie other epigenetic alterat…”
BackgroundResultInfluentialSelf-citationMaijenburg, M. W., Kleijer, M., Vermeul, K., Mul, E. P. J., van Alphen, F. P. J., van der Schoot, C. E., & Voermans, C. (2011) · Haematologica · doi:10.3324/haematol.2011.047753 · Cited by 105
“Cellular composition of BM changes during development(9) and aging.(8,10,14) The frequency of CFU-F declines with age,(8) but the effect on the composition of the MSC compartment is unknown.”
BackgroundHSC Aging and Senescent Immune Remodeling
Denkinger, M. D., Leins, H., Schirmbeck, R., Florian, M. C., & Geiger, H. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.10.008 · Cited by 107
“The question is still whether individual stem cells are prone to this or whether the increase in the number of myeloid-biased stem cells upon aging is responsible for the shift [53,54,85]”
A stem cell aging framework, from mechanisms to interventions
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Lymphohematopoietic progenitors do not have a synchronized defect with age‐related thymic involution
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“That is why the proportion of unfractionated BM cells expressing myeloid genes is increased in aged mice (Rossi et al., 2005).”
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Myeloid Cell Origins, Differentiation, and Clinical Implications
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“Gene expression changes and altered epigenetic landscapes have been demonstrated to contribute to these effects (60, 66, 67).”
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“1 B), consistent with known phenotypic HSC expansion with aging (Rossi et al., 2005).”
InfluentialMitochondria, immunosenescence and inflammaging: a role for mitokines?
Conte, M., Martucci, M., Chiariello, A., Franceschi, C., & Salvioli, S. (2020) · Seminars in Immunopathology · doi:10.1007/s00281-020-00813-0 · Cited by 105
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“For example, stem cells express high levels of many ABC/MDR transporter genes (Rossi et al., 2005; Zhou et al., 2001), which mediate drug efflux.”
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Changes in the Oligodendrocyte Progenitor Cell Proteome with Ageing
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“In common with other adult stem cells (56, 57), adult OPCs not only decrease the expression of proteins involved in stem cell maintenance, but also acquire a higher expression of proteins known to be markers of the terminal state of their lineage, the mature oligodendrocytes.”
BackgroundThe role of immunity in elderly cancer
Malaguarnera, L., Cristaldi, E., & Malaguarnera, M. (2009) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2009.06.002 · Cited by 103
“Recently, gene array data have showed hat the transcript from old HSC reflected a reduced capacity o differentiate into the lymphoid lineage, while exhibiting a ene expression profile that reflected an increased myeloid otential [25].”
BackgroundB-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
Transcriptome Analysis Identifies Regulators of Hematopoietic Stem and Progenitor Cells
Gazit, R., Garrison, B. S., Rao, T. N., Shay, T., Costello, J. C., Ericson, J., Kim, F., Collins, J. J., Regev, A., Wagers, A. J., et al. (2013) · Stem Cell Reports · doi:10.1016/j.stemcr.2013.07.004 · Cited by 96
“Although prior microarray studies have provided useful insights into HSC biology (Chambers et al., 2007; Forsberg et al., 2005, 2010; Rossi et al., 2005), it has proved challenging to cross-analyze data due to differences in experimental designs and technical methodologies.”
BackgroundSelf-citationThe RNA-binding protein YBX1 regulates epidermal progenitors at a posttranscriptional level
Kwon, E., Todorova, K. A., Wang, J., Horos, R., Lee, K. K., Neel, V., Negri, G. L., Sorensen, P. H. B., Lee, S. W., Hentze, M. W., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04092-0 · Cited by 98
Immunosenescence in multiple sclerosis: the identification of new therapeutic targets
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“sequences involving the commitment of progenitors, since myeloid differentiation is potentiated over lymphoid differentiation [10].”
BackgroundAging of hematopoietic stem cells is regulated by the stem cell niche
Wagner, W., Horn, P., Bork, S., & Ho, A. D. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2008.04.007 · Cited by 103
“HSC have a reduced ability to home to their niches upon transplantation into old versus young recipients (Rossi et al., 2005; Liang et al., 2005).”
The Effect of Bleeding on Hematopoietic Stem Cell Cycling and Self-Renewal
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“…stages, and activation status (38–42), KTSL (cid:4) /lo is an enduring HSC phenotype in the adult C57BL/Ka-Thy 1.1 mouse strain at all ages (43,44) and can be used to isolate both activated and steady-state HSCs from BM, spleen, and peripheral blood (3,15–17 , We analyzed the effect of a…”
InfluentialSelf-citationAcquired hematopoietic stem cell defects determine B-cell repertoire changes associated with aging
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“2 confirm earlier studies of WT mice (12) demonstrating that while capable of generating T cells and cells of other hematopoietic lineages, LT-HSCs from immunologically aged 3-83 animals are defective in B-cell genesis.”
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“Myeloid bias is well documented in the literature (Rossi et al., 2005), but molecular mechanisms are, thus far, elusive.”
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Interleukin-7 and Immunosenescence
Nguyen, V., Mendelsohn, A., & Larrick, J. W. (2017) · Journal of Immunology Research · doi:10.1155/2017/4807853 · Cited by 96
“Aging HSC demonstrate a reduced capacity for self-renewal [9, 10] and ability to differentiate along the lymphoid lineage [11] which is accompanied by an agedependent increase in cell-cycle inhibitor p16 [11].”
BackgroundAging in the lympho-hematopoietic stem cell compartment
Geiger, H., & Rudolph, K. L. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.03.010 · Cited by 103
Inhibition of B Lymphopoiesis by Adipocytes and IL-1–Producing Myeloid-Derived Suppressor Cells
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“(45) observed that aged HSCs exhibit downregulated expression of lymphoid-specific genes and upregulated expression of myeloid lineage genes.”
BackgroundAging-induced IL27Ra signaling impairs hematopoietic stem cells
He, H., Xu, P., Zhang, X., Liao, M., Dong, Q., Cong, T., Tang, B., Yang, X., Ye, M., Chang, Y., et al. (2020) · Blood · doi:10.1182/blood.2019003910 · Cited by 94
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“This is followed by staining of lineage-negative cells for stem cell related surface antigens and separation by fluorescent-activated cell sorting [47–67].”
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“Thisfinding is consistent with the effect of leukemia on theBMME reported in xenograft models, where leukemic cells alter the recipient BMME, which becomes more supportive of leukemicHSCs thannormalHSCs.50 Inboth the low and intermediateMDS engraftment models, the initial improvements in hematopoietic function in the…”
InfluentialDo 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
Hematopoietic Stem Cell Aging: Wrinkles In Stem Cell Potential
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“Another genome-wide methodology, expression profiling, has been used to identify molecular changes occur with age in HSC [12, 25].”
InfluentialAging as an Epigenetic Phenomenon
Ashapkin, V. V., Kutueva, L. I., & Vanyushin, B. F. (2017) · Current Genomics · doi:10.2174/1389202918666170412112130 · Cited by 94
“HSCs decrease function with age, showing as reduced self-renewal, hematopoiesis, and lymphopoiesis [121].”
BackgroundHematopoietic Stem Cell Development
Cullen, S. M., Mayle, A., Rossi, L., & Goodell, M. A. (2014) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-416022-4.00002-0 · Cited by 98
Mechanisms of hematopoietic stem cell aging
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“, 2000), skewed differentiation (Rossi et al., 2005; Cho et al., 2008; Dykstra et al., 2011), and an increase in the selection of clones that carry recurrent mutations (predominantly in genes that regulate epigenetic modification and gene expression; Busque et al.”
BackgroundConcise Review: Polarity in Stem Cells, Disease, and Aging
Florian, M. C., & Geiger, H. (2010) · Stem Cells · doi:10.1002/stem.481 · Cited by 94
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
“The myeloid bias appears to be at least in part cellautonomous, as adoptive transfer of young and old HSC into young, irradiated recipients recapitulates the agedependent bias towards myelopoiesis [1, 36, 50].”
BackgroundInfluentialHematopoietic Stem Cells and the Aging Hematopoietic System
Gazit, R., Weissman, I. L., & Rossi, D. J. (2008) · Seminars in Hematology · doi:10.1053/j.seminhematol.2008.07.010 · Cited by 84
Self-citationAging of hematopoietic stem cells: DNA damage and mutations?
Moehrle, B., & Geiger, H. (2016) · Experimental Hematology · doi:10.1016/j.exphem.2016.06.253 · Cited by 87
“Accumulation of gH2AX foci, indicative of persistent DNA DSBs [14]”
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
“Initial work profiling young and aged HSCs with microarrays identified ∼900 genes differentially expressed between young (2–3 mo old) and aged (22–24 mo old) mouse HSCs, with Gene Ontology (GO) terms enriched in signal transducer activity and receptor activity (Rossi et al., 2005).”
MethodInfluentialCognitive and Behavioral Consequences of Impaired Immunoregulation in Aging
Corona, A. W., Fenn, A. M., & Godbout, J. P. (2011) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-011-9313-4 · Cited by 87
“For example, results from a microarray study indicate that there was decreased expression of genes associated with lymphoid progenitor cells and increased expression of myeloid progenitor genes in the bone marrow of older mice compared to adults (Rossi et al. 2005).”
ResultSleep exerts lasting effects on hematopoietic stem cell function and diversity
McAlpine, C. S., Kiss, M. G., Zuraikat, F. M., Cheek, D. M., Schiroli, G., Amatullah, H., Huynh, P., Bhatti, M. Z., Wong, L. P., Yates, A. G., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20220081 · Cited by 92
“…regulated by stem-intrinsic epigenetic modifications to McAlpine et al. Journal of Experimental Medicine 2 of 15 Sleep alters prolonged HSPC function and diversity https://doi.org/10.1084/jem.20220081 lineage commitment genes (Morrison et al., 1996; Rossi et al., 2005; Dorshkind et al., 2020).”
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“As it is well known that age is a stressor to the hematopoietic and immune systems (Morrison et al. 1996; Sudo et al. 2000; Liang et al. 2005; Rossi et al. 2005, 2007; Chambers et al. 2007; Nijnik et al. 2007; Pang et al. 2011), it follows that hematopoietic failure in these TBI mice would be more…”
BackgroundAdult skull bone marrow is an expanding and resilient haematopoietic reservoir
Koh, B. I., Mohanakrishnan, V., Jeong, H., Park, H., Kruse, K., Choi, Y. J., Nieminen-Kelhä, M., Kumar, R., Pereira, R. S., Adams, S., et al. (2024) · Nature · doi:10.1038/s41586-024-08163-9 · Cited by 90
The ageing epigenome: Damaged beyond repair?
Sinclair, D. A., & Oberdoerffer, P. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2009.04.004 · Cited by 86
Tower, J. (2012) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.56 · Cited by 85
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 80
Self-citationOutside-in integrin signalling regulates haematopoietic stem cell function via Periostin-Itgav axis
Khurana, S., Schouteden, S., Manesia, J. K., Santamaria‐Martínez, A., Huelsken, J., Lacy‐Hulbert, A., & Verfaillie, C. M. (2016) · Nature Communications · doi:10.1038/ncomms13500 · Cited by 88
Numerous niches for hematopoietic stem cells remain empty during homeostasis
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Impact of age on the toxicity of immune checkpoint inhibition
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“632 ture is not part of an aging gene signature (Rossi et al., 2005; Chambers et al., 2007).”
BackgroundInfluentialJiang, S., Haider, H. K., Ahmed, R. P. H., Idris, N. M., Salim, A., & Ashraf, M. (2008) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2007.11.014 · Cited by 81
“Like other cells of an organism, MSCs are also subject to aging effects associated with decline in function and an imbalance between cell loss and cell renewal [15].”
BackgroundEpidermal stem cells are resistant to cellular aging
Stern, M. M., & Bickenbach, J. R. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00318.x · Cited by 79
“Old HSCs have been shown to have a gene expression profile significantly more biased toward the production of myeloid lineage cells (vs. lymphoid lineage), as compared to young HSCs (Rossi et al., 2005).”
BackgroundResultInfluentialCellular barcoding: A technical appraisal
Naik, S. H., Schumacher, T. N., & Perié, L. (2014) · Experimental Hematology · doi:10.1016/j.exphem.2014.05.003 · Cited by 80
“In contradiction to previous studies [40, 41], HSCs from old mice engrafted as efficiently as HSCs from younger mice, contradicting previous studies, although their cellular output was lower [28].”
ResultHohman, L. S., & Osborne, L. C. (2022) · Aging Cell · doi:10.1111/acel.13700 · Cited by 89
“Aged mice and humans exhibit an increased propensity for HSC skewing toward myeloid lineage differentiation over lymphopoiesis (Cho et al., 2008; Pang et al., 2011; Rossi et al., 2005), which is consistent with the reduction in naive T cell numbers and T cell receptor diversity seen in older individuals (Appay & Sauce…”
BackgroundResultInfluentialMultiple prethymic defects underlie age-related loss of T progenitor competence
Zediak, V. P., Maillard, I., & Bhandoola, A. (2007) · Blood · doi:10.1182/blood-2007-01-071605 · Cited by 79
“Absolute numbers of total LSK cells were stable, but numbers of HSC were increased and numbers of MPP were decreased with age (Figure 2B), consistent with previous work.(13,19,28) We also examined Ccr9 expression on the MPP population by flow cytometry and quantitative PCR to ask if thymus settling cells were further…”
BackgroundResultMontecino‐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
“transplantation into irradiated recipients (Rossi et al., 2005; Sudo et al., 2000).”
BackgroundResultBone marrow adipose tissue-derived stem cell factor mediates metabolic regulation of hematopoiesis
Zhang, Z., Huang, Z., Ong, B., Sahu, C., Zeng, H., & Ruan, H. (2019) · Haematologica · doi:10.3324/haematol.2018.205856 · Cited by 78
“Similar to obesity, aging is also associated with increased HSC numbers but decreased regenerative potential and skewed differentiation toward myeloid cells.(54,68,69) Both cell-intrinsic and cell-extrinsic mechanisms are accountable to these aged-related changes.”
BackgroundPeuß, R., Box, A., Chen, S., Wang, Y., Tsuchiya, D., Persons, J. L., Kenzior, A., Maldonado, E., Krishnan, J., Scharsack, J. P., et al. (2020) · Nature Ecology & Evolution · doi:10.1038/s41559-020-1234-2 · Cited by 80
Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches
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Bone Marrow-Derived Cells: The Influence of Aging and Cellular Senescence
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“Gene expression profiling of long-term HSC between young and old mice revealed a downregulation of genes mediating lymphoid differentiation ( Rossi et al. 2005 ).”
BackgroundYoung, Proliferative Thymic Epithelial Cells Engraft and Function in Aging Thymuses
Kim, M., Miller, C. M., Shadrach, J. L., Wagers, A. J., & Serwold, T. F. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1403158 · Cited by 74
“The loss of T cell potential of aged HSC, while apparent in some studies (15, 53), has been less consistently observed (54).”
ResultSelf-citationMiyamoto, K., Miyamoto, T. K., Kato, R., Yoshimura, A., Motoyama, N., & Suda, T. (2008) · Blood · doi:10.1182/blood-2008-05-159848 · Cited by 81
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 84
Pearce, D. J., Anjos‐Afonso, F., Ridler, C. M., Eddaoudi, A., & Bonnet, D. A. (2006) · Stem Cells · doi:10.1634/stemcells.2006-0405 · Cited by 77
Current perspectives on the cellular and molecular features of epigenetic ageing
Raj, K., & Horvath, S. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370220918329 · Cited by 77
Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult leukemia
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Hematopoietic stem cell aging and leukemia transformation
Díaz, P. A. C., Mistry, J. J., & Trowbridge, J. J. (2023) · Blood · doi:10.1182/blood.2022017933 · Cited by 83
Mimeault, M., & Batra, S. K. (2008) · Ageing Research Reviews · doi:10.1016/j.arr.2008.12.001 · Cited by 77
Epigenomic drivers of immune dysfunction in aging
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“HSC numbers actually increase with age, both in mice and humans, but these accumulated cells show reduced reconstitution potential (Morrison, Wandycz, Akashi, Globerson, & Weissman, 1996; Ogawa, Kitagawa, & Hirokawa, 2000; Pang et al., 2011; Rossi et al., 2005).”
BackgroundCauses 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 82
“Analysis of gene transcriptional profiles indicated that myeloid differentiation-linked and inflammation- and stress response-related genes were upregulated, but lymphopoiesis, DNA repair, and chromatin silencing genes were downregulated in aged HSCs [13,53].”
BackgroundResultClonal dynamics of haematopoiesis across the human lifespanPreprint
Mitchell, E., Chapman, M. S., Williams, N., Dawson, K. J., Mende, N., Calderbank, E. F., Jung, H., Mitchell, T. J., Coorens, T. H. H., Spencer, D. H., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.16.456475 · Cited by 74
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Hematopoietic stem cell ageing is uncoupled from p16INK4A-mediated senescence
Attema, J. L., Pronk, C. J. H., Norddahl, G. L., Nygren, J. M., & Bryder, D. (2009) · Oncogene · doi:10.1038/onc.2009.94 · Cited by 72
Self-citationTif1γ 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 77
Golomb, L., Sagiv, A., Pateras, I. S., Maly, A., Krizhanovsky, V, Gorgoulis, V. G., Oren, M., & Ben-Yehuda, A. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2015.21 · Cited by 71
“This is partially due to reduced lymphopoiesis, associated with events such as thymic involution(11) and age-dependent skewing of hematopoietic stem cell commitment toward myeloid lineage differentiation.(12,13) Age-dependent dysfunction of adaptive immunity can also result from intrinsic changes within different lymp…”
BackgroundGrebenciucova, E., & Berger, J. R. (2017) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-017-0771-9 · Cited by 75
Epigenetic regulation of hematopoietic stem cell aging
Beerman, I., & Rossi, D. J. (2014) · Experimental Cell Research · doi:10.1016/j.yexcr.2014.09.013 · Cited by 77
Self-citationReassessing the role of growth hormone and sex steroids in thymic involution
Min, H., Montecino‐Rodriguez, E., & Dorshkind, K. A. (2005) · Clinical Immunology · doi:10.1016/j.clim.2005.08.015 · Cited by 70
Immunophenotypic dissection of normal hematopoiesis
Órfão, A., Matarraz, S., Pérez‐Andrés, M., Almeida, J., Teodósio, C., Berkowska, M. A., & van Dongen, J. J. M. (2019) · Journal of Immunological Methods · doi:10.1016/j.jim.2019.112684 · Cited by 70
Evaluation of the Long-Term Reconstituting Subset of Hematopoietic Stem Cells with CD150
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Self-citationEffects of dietary restriction on hematopoietic stem-cell aging are genetically regulated
Ertl, R. P., Chen, J., Astle, C. M., Duffy, T. M., & Harrison, D. E. (2007) · Blood · doi:10.1182/blood-2007-01-069807 · Cited by 72
“This effect of aging in B6 may reduce the ability to fight infections by lowering the overall immune capabilities of the animal.(48,49) This is the first report of how aging affects the E/L ratio in BALB or F1 mice, where the trend with age is opposite that found in B6 mice.”
BackgroundEffects 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 72
Aging of the hematopoietic system
Snoeck, H. (2013) · Current Opinion in Hematology · doi:10.1097/moh.0b013e3283623c77 · Cited by 73
“Genome-wide expression studies did not reveal major changes in genes essential for maintenance of quiescence in HSCs [8,27], and HSC cycling does not increase with age.”
BackgroundInfluentialHeinonen, K. M., Vanegas, J. R., Lew, D., Krošl, J., & Perreault, C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019279 · Cited by 69
“selective reduction in the size of the LSK pool in aged mice, possibly through decreased age-related expansion [28].”
BackgroundLessons from the Crypt: HMGA1—Amping up Wnt for Stem Cells and Tumor Progression
Resar, L. M. S., Chia, L., & Xian, L. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-3045 · Cited by 69
“Prior studies showed declining Hmga1/HMGA1 in murine and human hematopoietic stem cells with aging (97, 98), which could contribute to decreasing regenerative function with age.”
Metadata
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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
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