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Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells
Open accessAbstract
Hematopoietic stem cell (HSC) populations change with aging, but the extent to which this is caused by qualitative versus quantitative alterations in HSC subtypes is unclear. Using clonal assays, in this study we show that the aging HSC compartment undergoes both quantitative and qualitative changes. We observed a variable increase of HSC pool size with age, accompanied by the accumulation of predominantly myeloid-biased HSCs that regenerate substantially fewer mature progeny than young myeloid-biased HSCs and exhibit reduced self-renewal activity as measured by long-term secondary transplantation. Old HSCs had a twofold reduction in marrow-homing efficiency and a similar decrease in functional frequency as measured using long-term transplantation assays. Similarly, old HSCs had a twofold reduced seeding efficiency and a significantly delayed proliferative response compared with young HSCs in long-term stromal cell co-cultures but were indistinguishable in suspension cultures. We show that these functional defects are characteristics of most or all old HSCs and are not indicative of a nonfunctional subset of cells that express HSC markers. Furthermore, we demonstrate that cells with functional properties of old HSCs can be generated directly from young HSCs by extended serial transplantation, which is consistent with the possibility that they arise through a process of cellular aging.
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In the citing paper
“Despite the increase in their number, myeloid-biased stem cells are not as robust as their young counterparts (24)”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [24]
In the citing paper
“That aged HSC are functionally impaired compared with their young counterparts upon transplantation in young mice”
From Aging of hematopoietic stem cells (2018) · cites this paper as [10]
In the citing paper
“the functional heterogeneity of the HSC population increases with age.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [10]
In the citing paper
“in aged mice that display an overall increase in HSC pool size”
From Aging of hematopoietic stem cells (2018) · cites this paper as [10]
In the citing paper
“individual HSCs behave very differently.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [10]
In the citing paper
“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 [10]
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Cites
Hu, Y., & Smyth, G. K. (2009) · Journal of Immunological Methods · doi:10.1016/j.jim.2009.06.008 · Cited by 2,084 · cited 1×
“…to Gr-1+SSChi cells at 24 wk after transplant were considered to be repopulated with HSCs and were counted as positive for the purposes of the limiting dilution calculation, performed using the Web-based calculator provided at http://bioinf.wehi.edu .au/software/elda/ (Hu and Smyth, 2009).”
MethodWilson, A., Laurenti, E., Oser, G., van der Wath, R. C., Blanco-Bose, W., Jaworski, M., Offner, S., Dunant, C. F., Eshkind, L., Bockamp, E., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.048 · Cited by 1,908 · cited 1×
“To confirm the utility of this measurement, we sorted three LSK subpopulations from young BM: LSK4834E+150+, LSK4834+150, and LSK48+34+150, which are known to contain HSCs, more primitive multipotent progenitors (MPPs), and less primitive MPPs, respectively (Wilson et al., 2008).”
MethodCell 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 2×
“…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).”
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 · cited 5×
“Consistent with earlier studies (Morrison et al., 1996; Sudo et al., 2000; Rossi et al., 2007b), the median proportion of LinloSca1+cKit+ (LSK) cells within the BM increased 1.9-fold in old mice (Fig.”
BackgroundResultInfluentialIsolation of Single Human Hematopoietic Stem Cells Capable of Long-Term Multilineage Engraftment
Notta, F., Doulatov, S., Laurenti, E., Poeppl, A., Jurisica, I., & Dick, J. E. (2011) · Science · doi:10.1126/science.1201219 · Cited by 919 · cited 1×
“Exciting recent developments in purification and assays for human HSCs (Notta et al., 2011) finally open up the possibility for similar interrogation of the aged human HSC pool at a clonal level.”
BackgroundIn vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days
Pillay, J., den Braber, I., Vrisekoop, N., Kwast, L. M., de Boer, R. J., Borghans, J. A. M., Tesselaar, K., & Koenderman, L. (2010) · Blood · doi:10.1182/blood-2010-01-259028 · Cited by 873 · cited 1×
“As a strict measure for long-term, active hematopoiesis, we considered a mouse to be transplanted with an HSC only if there was a minimum 1% donor contribution to the short-lived (Pillay et al., 2010) granulocyte population (defined as Gr-1+SSChi) at 24 wk after transplant.”
BackgroundThe 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 · cited 5×
“…expressing HSC-associated markers is contaminated with primitive progenitors that are detected by in vitro assays but lack repopulating ability in vivo (Sudo et al., 2000) or that HSCs from old mice have a homing and/or engraftment defect and therefore remain undetected (Morrison et al., 1996).”
BackgroundResultInfluentialAging 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
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 · cited 8×
“…expressing HSC-associated markers is contaminated with primitive progenitors that are detected by in vitro assays but lack repopulating ability in vivo (Sudo et al., 2000) or that HSCs from old mice have a homing and/or engraftment defect and therefore remain undetected (Morrison et al., 1996).”
BackgroundResultInfluentialBeerman, 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
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Items 301–400 of 494
Haematopoietic ageing through the lens of single-cell technologies
Strzelecka, P. M., & Damm, F. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.047340 · Cited by 10
“Single-cell RNA sequencing (scRNAseq) deciphers the gene expression changes in individual HSCs associated with the ageing phenotype, such as lineage bias, imbalance between self-renewal (Box 1) and differentiation, and declined engraftment in transplantation assays (Dykstra et al., 2011).”
BackgroundMicro‐environment alterations through time leading to myeloid malignancies
Nyamondo, K., & Wheadon, H. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15924 · Cited by 10
“Studies indicate these changes may originate from cell-intrinsic changes (Dykstra et al., 2011), such as epigenetic deregulation (Chambers et al., 2007), replication stress (Flach et al., 2014) and deficiencies in DNA repair.”
Molecular Mechanisms of the Aging Process and Rejuvenation
Shiomi, N. (2016) · InTech eBooks · doi:10.5772/61700 · Cited by 11
Ratliff, M., Garton, J. W., James, J. A., & Webb, C. F. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00198-6 · Cited by 11
Replenishing B lymphocytes in health and disease
Zhang, Q., Iida, R., Shimazu, T., & Kincade, P. W. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.12.007 · Cited by 10
Yang, F., Nourse, C., Helgason, G. V., & Kirschner, K. (2023) · HemaSphere · doi:10.1097/hs9.0000000000000895 · Cited by 12
“Dykstra et al 16 reported an increase in LSK cells in the bone marrow of old mice with a simultaneous increase in purer populations marked by CD48 − CD34 − EPCR + CD150 + .”
Measuring the Aging Process in Stem Cells
Liu, Y., Zant, G. E. V., & Liang, Y. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1785-3_3 · Cited by 9
“In the mouse model, HSCs and HPCs are enriched in the population negative for the markers of all differentiated lineages cells (Lineage-) and positive for stem cell markers Sca-1 and c-Kit (LSK cells) (38).”
BackgroundMethodInfluentialGrowing old in the age of heterogeneity: the perils of shifting clonality
Gustafsson, K. U., & Scadden, D. T. (2019) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000513 · Cited by 9
“Although the immunophenotypic HSC pool size is thought to increase, the regenerative ability on a per cell basis is reduced [24,26,29,30] and the self-renewing ability of HSCs is impaired [24,27 && ].”
BackgroundHe, L., Beghi, F., Baral, V., Dépond, M., Zhang, Y., Joulin, V., Rueda, B. R., Gonin, P., Foudi, A., Wittner, M., et al. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.06.002 · Cited by 9
The impact of clonal diversity and mosaicism on haematopoietic function in Fanconi anaemia
Hughes, A. D., & Kurre, P. (2021) · British Journal of Haematology · doi:10.1111/bjh.17653 · Cited by 10
“Even as their immunophenotypic number increases, the HSC of aged mice exhibits functional compromise, with reduced marrowhoming efficiency, seeding efficiency and delayed proliferative response, compared to the HSC of young mice.(40) Conceptually, the entire HSC pool consists of a finite number of distinct HSC, each h…”
BackgroundLoss of the Fanconi anemia–associated protein NIPA causes bone marrow failure
Kreutmair, S., Erlacher, M., Andrieux, G., Istvánffy, R., Rudorf, A., Zwick, M., Rückert, T., Pantić, M., Poggio, T., Shoumariyeh, K., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci126215 · Cited by 9
“, who correlated BM reconstitution efficiency indirectly with age, finding 2- to 3-fold-lower engraftment of old compared with young HSCs (46, 47).”
ResultAberrant engagement of P-selectin drives hematopoietic stem cell aging in mice
Yang, D., Skinder, N., Kao, Y.-R., Chen, J., Thiruthuvanathan, V. J., Svendsen, A. F., Zhang, C., Dethmers-Ausema, B., Weersing, E., Maryanovich, M., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00880-8 · Cited by 11
“Aging-associated intra-and inter-organismic molecular and cell-functional phenotypes do not emerge synchronously—hallmarked by an increasing degree of biological heterogeneity including at the HSC level 1–4 , 6 .”
Harnett, M. M., Doonan, J., Lumb, F. E., Crowe, J., Damink, R. O., Buitrago, G., Duncombe-Moore, J., Wilkinson, D., Suckling, C. J., Selman, C., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.953053 · Cited by 8
“the levels of HSCs between d340 and d500 in HCD-fed animals, previous studies on C57BL/6 mice showed that Chow-fed mice typically exhibited elevated levels of HSCs displaying loss of functionality between 18-24 months (d547-730), at which point such dysregulation was not further enhanced in mice experiencing a lifelon…”
Neutrophil-Mediated Progression of Mild Cognitive Impairment to Dementia
Cho, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914795 · Cited by 9
“Hematopoietic stem cells (HSCs) of aged mice are changed via myelopoiesis and lymphopoiesis in the bone marrow [53,54].”
BackgroundChen, J., Bryant, M., Dent, J. J., Sun, Y., Desierto, M. J., & Young, N. S. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.10.016 · Cited by 8
“…in old Terc−/− and old Terc+/+ animals was in general agreement with previous observations of age-related increases in HSC numbers (Chen, 2004; Dykstra et al., 2011; Morrison et al., 1996), and is consistent with a recent report in which KSLs cells were expanded in 12-month old G1 Terc−/−…”
ResultTristetraprolin limits age-related expansion of myeloid-derived suppressor cells
Kwack, K. H., Zhang, L., Kramer, E. D., Thiyagarajan, R., Lamb, N. A., Arao, Y., Bard, J., Seldeen, K. L., Troen, B. R., Blackshear, P. J., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1002163 · Cited by 8
Ruf, F., Schreck, C., Wagner, A., Grziwok, S., Pagel, C., Romero, S., Kieslinger, M., Shimono, A., Peschel, C., Götze, K. S. S., et al. (2016) · Stem Cells · doi:10.1002/stem.2416 · Cited by 9
Genetic Barcodes Facilitate Competitive Clonal Analyses In Vivo
Aranyossy, T., Thielecke, L., Glauche, I., Fehse, B., & Cornils, K. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.124 · Cited by 7
“5% total blood or BM contribution.(40,53,54) As the aim was to compare clonal dynamics of the different constructs, a relative threshold applicable over all vector constructs was required.”
Zheng, X., Zhang, G., Gong, Y., Ning, X., Bai, Z., He, J., Zhou, F., Ni, Y., Lan, Y., & Liu, B. (2019) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2019.10.005 · Cited by 8
Aging and immunity: the age-old tangoPreprint
Fernández-Maestre, I., Harris, A. S., & Amor, C. (2025) · Genes & Development · doi:10.1101/gad.352644.125 · Cited by 8
“Paradoxically, despite these functional impairments, HSCs increase in numbers, which shows an “ off-kilter ” production within the hematopoietic system (Dykstra et al. 2011).”
Prostaglandin E2 Enhances Aged Hematopoietic Stem Cell Function
Patterson, A. M., Plett, P. A., Sampson, C. H., Simpson, E. R., Liu, Y., Pelus, L. M., & Orschell, C. M. (2021) · Stem Cell Reviews and Reports · doi:10.1007/s12015-021-10177-z · Cited by 7
Metabolic regulation of aged hematopoietic stem cells: key players and mechanisms
Karimnia, N., Harris, J., Heazlewood, S. Y., Cao, B., & Nilsson, S. K. (2023) · Experimental Hematology · doi:10.1016/j.exphem.2023.09.006 · Cited by 7
Skinder, N., Fernández, I. S., Dethmers-Ausema, A., Weersing, E., & de Haan, G. (2023) · Blood Advances · doi:10.1182/bloodadvances.2023011585 · Cited by 8
“4,6 Single-cell division assay.”
Cheminant, J. R., Deering‐Rice, C. E., Massa, C. B., Adhikari, U., Noll, J., Reilly, C. A., & Venosa, A. (2025) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00261.2024 · Cited by 9
Do hematopoietic stem cells get old?
Jung, J., Buisman, S. C., & de Haan, G. (2016) · Leukemia · doi:10.1038/leu.2016.301 · Cited by 7
Schuster, T., & Geiger, H. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.801507 · Cited by 6
Gagnon, M.-F., Provost, S., Sun, M., Ayachi, S., Buscarlet, M., Mollica, L. R., Szuber, N., Dubé, M., & Busque, L. (2023) · Blood Advances · doi:10.1182/bloodadvances.2022008793 · Cited by 8
Inflammaging and age-associated diseases
Manabe, I. (2017) · Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics · doi:10.3143/geriatrics.54.105 · Cited by 7
Ostrander, E. L., Koh, W. K., Mallaney, C., Kramer, A. C., Wilson, W. C., Zhang, B., & Challen, G. A. (2017) · Experimental Hematology · doi:10.1016/j.exphem.2017.09.004 · Cited by 8
Graffmann, N., Brands, J., Görgens, A., Castro, S. V. D. C., Santourlidis, S., Reckert, A., Michele, I., Ritz‐Timme, S., Fischer, J., Adjaye, J., et al. (2015) · Stem Cells and Development · doi:10.1089/scd.2014.0435 · Cited by 6
“Our investigation of the expression of key hematopoietic transcription factors in the context of the respective histone modification pattern revealed some parallels to the described age-associated myeloid bias of murine and human HSCs [5,7–9 , 11 ].”
Modeling GATA2 deficiency in mice: the R396Q mutation disrupts normal hematopoiesis
Hall, T., Mehmood, R., da Bandeira, D. S., Cotton, A., Klein, J. D., Pruett‐Miller, S. M., Izraeli, S., Clements, W. K., & Crispino, J. D. (2025) · Leukemia · doi:10.1038/s41375-024-02508-z · Cited by 6
“For instance, increased mitochondrial activity has been shown to be associated with HSC aging [55], and aged HSCs lose self-renewal capacity and are myeloid-biased [47, 56, 57].”
A Senescent Cluster in Aged Human Hematopoietic Stem Cell Compartment as Target for Senotherapy
Poisa-Beiro, L., Landry, J. J. M., Yan, B., Kardorff, M., Eckstein, V., Villacorta, L., Krammer, P. H., Zaugg, J. B., Gavin, A., Beneš, V., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26020787 · Cited by 7
Vukadin, L., Park, B., Mohamed, M., Li, H., Elkholy, A., Torrelli-Diljohn, A., Kim, J., Jeong, K., Murphy, J. M., Harvey, C. A., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.175053 · Cited by 6
Emerging Evidence of the Significance of Thioredoxin-1 in Hematopoietic Stem Cell Aging
Jabbar, S., Mathews, P., & Kang, Y. (2022) · Antioxidants · doi:10.3390/antiox11071291 · Cited by 6
Zeng, X., Li, X., Shao, M., Xu, Y., Shan, W., Wei, C., Li, X., Wang, L., Hu, Y., Zhao, Y., et al. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.745786 · Cited by 6
“Hematopoietic stem cell (HSC) aging is accompanied by reduced self-renewal ability, myeloid-biased differentiation, impaired homing capacity and other defects in hematopoietic reconstitution function (Liang et al., 2005; Rossi et al., 2005; Dykstra et al., 2011; Li et al., 2020).”
BackgroundTarget practice: Opportunities for therapeutic intervention in CHIP and CCUS
Mohammad, A., Mascarenhas, J. O., Marcellino, B. K., & Nathan, D. I. (2025) · Blood Reviews · doi:10.1016/j.blre.2025.101323 · Cited by 5
Critical role of niche S100A8 for acute myeloid leukemia progression and hematopoiesis regeneration
Zhou, F., Liu, X., Wu, J., Li, X., Pan, R., Liu, L., Huang, T., Ma, L., Chen, G., Wang, Q., et al. (2025) · Blood Advances · doi:10.1182/bloodadvances.2024015762 · Cited by 5
Mechanistic insights into stem cell aging: Pathways and processes
Fauzi, A., Wong, C. Z. E., Tee, P. Y. E., Yau, A. W. N., Rashid, E. A., Tang, Y. Q., & Chia, A. Y. Y. (2026) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2026.112160 · Cited by 6
E3 ubiquitin ligase on the biological properties of hematopoietic stem cell
Zhan, Q., Wang, J., Zhang, H., & Zhang, L. (2023) · Journal of Molecular Medicine · doi:10.1007/s00109-023-02315-6 · Cited by 5
“For young mouse recipients receiving serial transplants, stem cells derived from BM of older mice have a much lower self-renewal capacity compared to those of young mice [123].”
BackgroundHussain, A., Deleuze, V., Kebriti, L. E., Turali, H., Pirot, N., Glasson, Y., Mathieu-Mahul, D., & Pinet, V. (2020) · Stem Cells · doi:10.1002/stem.3286 · Cited by 4
Clonal-level responses of functionally distinct hematopoietic stem cells to trophic factors
Mallaney, C., Kothari, A., Martens, A., & Challen, G. A. (2013) · Experimental Hematology · doi:10.1016/j.exphem.2013.11.015 · Cited by 5
“For example, lymphoid-biased HSCs predominate in the fetal liver [12] while myeloid-biased HSCs accumulate with age [3–5], although it may be more appropriate to refer to aged HSCs as “lymphoid-deficient” [12, 36].”
BackgroundThe non-canonical Wnt pathway leads to aged dendritic cell differentiation
Zhou, H., & Wu, L. (2018) · Cellular and Molecular Immunology · doi:10.1038/cmi.2017.169 · Cited by 5
Rožman, P. J. (2019) · Rejuvenation Research · doi:10.1089/rej.2018.2164 · Cited by 5
“83,84 88 Besides, various studies document that BM-and mobilized peripheral blood-derived HSCs can engraft into various organs, including the spleen, mesenteric lymph nodes, heart, kidney, liver, pancreas, central nervous system, lung epithelial cells, skin, eye, and gastrointestinal tract, where…”
Methylome of human senescent hematopoietic progenitors
Capone, S., Colombo, A., Johnson, B. K., Triche, T. J., & Ramsingh, G. (2018) · Experimental Hematology and Oncology · doi:10.1186/s40164-018-0123-8 · Cited by 5
Immunosenescence, Inflammaging, and Their Implications for Cancer and Anemia
Paudel, S., Sharma, P., & Puri, N. (2019) · Springer eBooks · doi:10.1007/978-981-13-3585-3_14 · Cited by 6
Hampton, K., Polski-Delve, A. N., Hellmich, C., & Rushworth, S. A. (2025) · Stem Cells · doi:10.1093/stmcls/sxaf053 · Cited by 4
Cancer and aging: complex associations and therapeutic targets
Liang, J., Zang, S., Zhe, W. A. N. G., & Zhang, R. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00423-6 · Cited by 4
Aging of hematopoietic stem cells: Insight into mechanisms and consequences
Chatterjee, B., & Thakur, S. S. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820071-1.00016-5 · Cited by 4
Epigenetic modifier SMCHD1 maintains a normal pool of long-term hematopoietic stem cells
Kinkel, S., Liu, J. J., Beck, T. J., Breslin, K. A., Iminitoff, M., Hickey, P. F., & Blewitt, M. E. (2022) · iScience · doi:10.1016/j.isci.2022.104684 · Cited by 4
“An increase in HSC number and frequency is a hallmark of the aged hematopoietic system, although these aged HSCs are functionally impaired (Chambers et al., 2007b; Dykstra et al., 2011; Rossi et al., 2005); this normal HSC expansion was not evident in Smchd1-deleted females.”
BackgroundSomuncular, E., Su, T.-Y., Dumral, Ö., Johansson, A., & Luc, S. (2023) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szad057 · Cited by 4
“Therefore, to estimate the frequency of functional HSCs in the CD49b and CD229 fractionated subsets, we used limiting dilution calculation, 18,21 which predicted the lowest frequency in CD49b + CD229 + cells, consistent with lower reconstituting ability and reduced HSC activity (Fig.”
Sirtuins and the prevention of immunosenescence
Lasigliè, D. (2021) · Vitamins and hormones · doi:10.1016/bs.vh.2020.12.011 · Cited by 5
Postnatal conservation of human blood- and marrow-specific CD34+ hematopoietic phenotypes
Hammond, C. A., & Eaves, C. J. (2022) · Experimental Hematology · doi:10.1016/j.exphem.2022.03.004 · Cited by 5
The Problem of Stem Cell Definition
Vorotelyak, E. A., Vasiliev, A. V., & Terskikh, V. V. (2020) · Cell and Tissue Biology · doi:10.1134/s1990519x20030086 · Cited by 4
Noncanonical Wnt Comes of Age in Hematopoietic Stem Cells
Verovskaya, E. V., & de Haan, G. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.11.009 · Cited by 4
“Moreover, HSCs from old mice demonstrate a reduced ability to home and engraft bone marrow niches, and they 642 Cell Stem Cell 13, December 5, 2013 ª2 show increased mobilization in response to cytokines (Dykstra et al., 2011; Geiger et al., 2013).”
BackgroundZhang, Y. W., & Cabezas‐Wallscheid, N. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9574-5_15 · Cited by 4
Alteration of long- and short-term hematopoietic stem cell ratio causes myeloid-biased hematopoiesisPreprint
Nishi, K., Sakamaki, T., Nagasaka, A., Kao, K. S., Sadaoka, K., Asano, M., Yamamoto, N., Takaori‐Kondo, A., & Miyanishi, M. (2024) · eLife · doi:10.7554/elife.95880 · Cited by 6
“…clones Numerous studies have claimed that the myeloid-skewed phenotype observed in PB of aged mice is caused by myeloid-biased HSC clones selectively expanded from HSCs with originally heterogeneous differentiation potentials ( Beerman et al., 2010 ; Dykstra et al., 2011 ; Sudo et al., 2000 ).”
InfluentialMorikawa, T., Fujita, S., Sugiura, Y., Tamaki, S., Haraguchi, M., Shiroshita, K., Watanuki, S., Kobayashi, H., Kanai-Sudo, H., Naito, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60515-9 · Cited by 3
The systemic costs of hematopoietic stem cell aging
Puri, G., & Blanc, R. S. (2025) · Development · doi:10.1242/dev.205103 · Cited by 3
“Additionally, aged HSCs exhibit skewed differentiation toward myeloid lineages, producing fewer lymphoid progenitors (B and T cells) and more megakaryocytic cells (Dykstra et al., 2011; Pang et al., 2011; Grover et al., 2016; Aksöz et al., 2024).”
Clausell-Tormos, J. (2014) · Journal of Nanomedicine & Nanotechnology · doi:10.4172/2157-7439.1000191 · Cited by 3
“However, cell-to-cell differences have been reported even for supposedly homogenous cell populations [2-4], and the ensemble behavior of a population may not represent the behavior of individual cells bearing distinct features.”
BackgroundAnti-ageing antibodies revive the immune system
Kasu, Y. A. T., & Signer, R. A. J. (2024) · Nature · doi:10.1038/d41586-024-00680-x · Cited by 3
Loss of P2Y14 results in an arresting response to hematological stress
Garrison, B. S., & Rossi, D. J. (2014) · Journal of Clinical Investigation · doi:10.1172/jci76626 · Cited by 4
Roolf, C., Kretzschmar, C., Timmer, K., Sekora, A., Knuebel, G., Escobar, H. M., Fuellen, G., Ibrahim, S. M., Tiedge, M., Baltrusch, S., et al. (2016) · In Vivo · doi:10.21873/invivo.10991 · Cited by 3
Vangl2 Promotes Hematopoietic Stem Cell Expansion
Bouali, S., Hétu-Arbour, R., Gardet, C., & Heinonen, K. M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.760248 · Cited by 2
Pan, W. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91617-2.00003-1 · Cited by 3
Towards a Mechanistic Understanding of Epigenetic Dynamics
Przybilla, J., Rohlf, T., & Galle, J. (2015) · Translational bioinformatics · doi:10.1007/978-94-017-9927-0_7 · Cited by 3
Young, K. A., Eudy, E., Bell, R. K., Loberg, M. A., Stearns, T. M., Velten, L., Haas, S. F., & Trowbridge, J. J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.11.198846 · Cited by 3
Alzheimer’s disease causes bone marrow myelopoiesis dysfunctionPreprint
Abellanas, M. A., Basurco, L., Purnapatre, M., Burgaletto, C., Castellani, G., Colaiuta, S. P., Ramos, J. M. P., Ibraheem, A., Murad, S., Antonello, P., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.06.680030 · Cited by 3
Xiu, Y., Xiong, M., Yang, H., Wang, Q., Zhao, X. Q., Long, J., Liang, F., Liu, N., Chen, F., Gao, M., et al. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150661 · Cited by 2
Xie, Y., Qiao, X., Wu, H., Hua, Y., Li, B., Ding, N., Pang, J., Zhang, M., Xi, W., Deng, K., et al. (2026) · Blood · doi:10.1182/blood.2026033155 · Cited by 2
Aging and “rejuvenation” of resident stem cells — a new way to active longevity?
Baklaushev, V. P., Samoilova, E. M., Анатольевич, К. В., & Yusubalieva, G. M. (2022) · Journal of clinical practice · doi:10.17816/clinpract104999 · Cited by 2
How CBX proteins regulate normal and leukemic blood cells
de Groot, A. P., & de Haan, G. (2024) · FEBS Letters · doi:10.1002/1873-3468.14839 · Cited by 4
Tao, S., Qiu, X., Wang, Y., Qiu, R., Yu, C., Sun, M., Liu, L., Tao, Z., Zhang, L., & Tang, D. (2024) · Stem Cell Reviews and Reports · doi:10.1007/s12015-024-10754-y · Cited by 2
“Multiple factors, such as hematopoietic stem cell (HSC) functioning and the recipient’s environment, affect post-transplant hematopoiesis [ 1, 3–5].”
Shahaf, G. L., Hazanov, H., Averbuch, D., Amu, S., Ademokun, A., Wu, Y.-C. B., Dunn‐Walters, D. K., Chiodi, F., & Mehr, R. (2014) · International perspectives on aging · doi:10.1007/978-3-319-06650-9_4 · Cited by 2
Sharpe, M. E., Leoni, G., & Hyllner, J. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.64245-9 · Cited by 2
Gotzhein, F., Aranyossy, T., Thielecke, L., Sonntag, T., Thaden, V., Fehse, B., Müller, I., Glauche, I., & Cornils, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063160 · Cited by 2
The Potential Role of Stem Cell Reprogramming in Antiaging
Yılmaz, B. O., & Erkan, M. (2018) · Springer eBooks · doi:10.1007/978-981-13-1699-9_3 · Cited by 2
Alteration of long and short-term hematopoietic stem cell ratio causes myeloid-biased hematopoiesisPreprint
Nishi, K., Sakamaki, T., Nagasaka, A., Kao, K. S., Sadaoka, K., Asano, M., Yamamoto, N., Takaori‐Kondo, A., & Miyanishi, M. (2024) · eLife · doi:10.7554/elife.95880.2 · Cited by 2
González-Meljem, J. M., Haston, S., Gallage, S., & Innes, A. J. (2018) · Springer eBooks · doi:10.1007/978-3-319-95387-8_3 · Cited by 1
Ageing and its role in modulating healthy and tumour-associated macrophages
Duong, L., Jackaman, C., & Nelson, D. J. (2024) · Ageing and Cancer Research & Treatment · doi:10.37155/2972-4759-2024-02-01-1 · Cited by 1
Iwanami, S., Sato, T., Haeno, H., Xu, L., Imamura, K., Ooehara, J., Lan, X., Nakauchi, H., Iwami, S., & Yamamoto, R. (2025) · iScience · doi:10.1016/j.isci.2025.112547 · Cited by 1
Yu, C., Qiu, X., Tao, S., Wu, Y., He, S., Wang, Q., Tang, D., & Wang, Y. (2025) · Biogerontology · doi:10.1007/s10522-025-10263-6 · Cited by 3
“Another central hallmark of aged HSCs is their skewing towards myeloid cell differentiation, providing more myeloid progenitor cells and fewer lymphoid progenitor cells compared to young HSCs (Geiger et al. 2013; Dykstra et al. 2011).”
Clonal hematopoiesis: linking hematopoietic stem cell aging with age-related diseases
Li, Z., Zhou, Z., You, W., Xiao, F., Ju, Z., & Chen, Z. (2025) · Oral Science and Homeostatic Medicine · doi:10.26599/oshm.2025.9610016 · Cited by 1
Ageing Through the Looking‐Glass: The Different Flavours of Clonal Haematopoiesis
Singh, J., Curtis, D. J., Thảo, L. T. P., Wood, E. M., & McQuilten, Z. (2026) · Aging Cell · doi:10.1111/acel.70425 · Cited by 1
“Functional changes in HSCs with age are thought to be predominantly mediated by intrinsic mechanisms, as younger HSCs engraft better than older HSCs when transplanted into mice (de Haan and Lazare 2018; Dykstra et al. 2011; Morrison et al. 1996).”
Chromatin reorganization drives overexpression of a Btaf1 variant underpinning hematopoietic aging
Zong, L., Park, B., Cao, Y., Ma, F., Tekinturhan, F., Kuribayashi, W., Zhao, K., & Beerman, I. (2026) · Nature Communications · doi:10.1038/s41467-026-70787-4 · Cited by 1
Inflammaging and the role of micronutrients as immunomodulators: a pathway to healthy aging
Tan, S. S. L., Garg, V., Dhiman, A., Bansal, N., & Conway, P. L. (2026) · Immunity & Ageing · doi:10.1186/s12979-026-00569-5 · Cited by 1
“However, in vivo study in mice demonstrated that during aging HSCs exhibit a skewed differentiation toward the myeloid lineage, leading to reduced production of lymphoid cells [36] (Fig.”
Aging mechanisms and rejuvenation strategies for hematopoietic stem cells
Zhang, Y., Xu, Y., Shi, W., Cao, D., Guo, D.-A., & Yue, R. (2026) · Genome biology · doi:10.1186/s13059-026-04119-6 · Cited by 1
“A notable paradox is the coexistence of declining self-renewal capacity with an expansion in phenotypically defined HSC numbers [49].”
Aging of hematopoietic stem cells is inconsequential to progenitor cell function
Myers, J., Worthington, A. K., Poscablo, D. M., Medina, P., Chattopadhyaya, S., Mogharrab, R., Rommel, M. G. E., & Forsberg, E. C. (2026) · Stem Cell Reports · doi:10.1016/j.stemcr.2026.102965 · Cited by 3
Gensheimer, J., LaGosh, J., Moulton, E. R., Sun, V., de Barros, S. C., Montecino‐Rodriguez, E., Yiu, G., Yuan, X., Dorshkind, K. A., & Gm, C. (2026) · Aging Cell · doi:10.1111/acel.70615 · Cited by 1
“The HSC pool changes dramatically with age, increasing both in number and myeloid-biased differentiation (Cho et al. 2008; Dykstra et al. 2011).”
Vitamin C attenuates primate bone marrow aging at the molecular and progenitor level
Ye, Y., Zhang, H., Xin, Z., Sun, W., Liu, L., Xiong, M., Zhao, H., Zhang, Y., Geng, J., Zhao, L., et al. (2026) · Cell stem cell · doi:10.1016/j.stem.2026.06.006 · Cited by 1
What do we know about the participation of hematopoietic stem cells in hematopoiesis?
Дризе, Н. И., & Петинати, Н. А. (2015) · F1000Research · doi:10.12688/f1000research.6459.1 · Cited by 1
Development and aging of resident endothelial stem cells in pre-existing blood vessels
Rahmawati, F. N., & Takakura, N. (2025) · Experimental Hematology · doi:10.1016/j.exphem.2025.104795 · Cited by 1
Alteration of long- and short-term hematopoietic stem cell ratio causes myeloid-biased hematopoiesis
Nishi, K., Sakamaki, T., Nagasaka, A., Kao, K. S., Sadaoka, K., Asano, M., Yamamoto, N., Takaori‐Kondo, A., & Miyanishi, M. (2025) · eLife · doi:10.7554/elife.95880.4 · Cited by 1
The novel tumor suppressor AIRAPL regulates IGF1R proteostasis
Osorio, F. G., Freije, J. M. P., & López-Otı́n, C. (2016) · Cell Cycle · doi:10.1080/15384101.2016.1151725 · Cited by 2
DRAG in situ barcoding reveals an increased number of HSPCs contributing to myelopoiesis with agePreprint
Urbanus, J. H. M., Cosgrove, J., Beltman, J. B., Elhanati, Y., Moral, R. D. A., Conrad, C., van Heijst, J. W. J., Tubeuf, E., Velds, A., Kok, L., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.06.519273 · Cited by 1
Alteration of long and short-term hematopoietic stem cell ratio causes myeloid-biased hematopoiesisPreprint
Nishi, K., Sakamaki, T., Nagasaka, A., Kao, K. S., Sadaoka, K., Asano, M., Yamamoto, N., Takaori‐Kondo, A., & Miyanishi, M. (2024) · eLife · doi:10.7554/elife.95880.1 · Cited by 2
Zhou, F., Liu, X., Wu, J., Li, X., Pan, R., Liu, L., Huang, T., Ma, L., Chen, G., Wang, Q., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-4374015/v1 · Cited by 1
Platelet Factor 4 (PF4) Regulates Hematopoietic Stem Cell AgingPreprint
Zhang, S., Ayemoba, C. E., Staulo, A. M. D., Joves, K., Patel, C. M., Leung, E. H. W., Ong, S., Nerlov, C., Maryanovich, M., Chronis, C., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.25.625252 · Cited by 1
Alteration of long and short-term hematopoietic stem cell ratio causes myeloid-biased hematopoiesisPreprint
Nishi, K., Sakamaki, T., Nagasaka, A., Kao, K. S., Sadaoka, K., Asano, M., Yamamoto, N., Takaori‐Kondo, A., & Miyanishi, M. (2025) · eLife · doi:10.7554/elife.95880.3 · Cited by 1
Stolz, A., Xuan, C., Freitas, C., Chelbi, R., Ait-Ougouram, H., Fandrei, D., Ye, M., Nelson, E., Maillard, C., Bohm, M., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.21.665900 · Cited by 4
Proteostasis Stress Drives Stem Cell Aging, Clonal Hematopoiesis and LeukemiaPreprint
Zhou, F., Le, M. K., Wang, H. C., Yang, W., Wang, H., Tiwari, A., Cen, X., Sunshine, M. J., Magee, J. A., & Signer, R. A. J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.27.690982 · Cited by 1
Metadata
- Authors
- Dykstra, B., Olthof, S., Schreuder, J., Ritsema, M., & de Haan, G.
- Affiliations
- University Medical Center Groningen (NL)
- Department of Cell Biology 1 ; and 2
- Corresponding author
- Dykstra, Brad
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2011-11-21
- Volume
- 208
- Issue
- 13
- Pages
- 2691-2703
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC3244040
- OpenAlex
- W2103911902
- Cited by
- 494
- References
- 38
- Citations by year
- 2026: 26 · 2025: 34 · 2024: 35 · 2023: 42 · 2022: 38 · 2021: 42 · 2020: 41 · 2019: 36 · 2018: 40 · 2017: 26 · 2016: 36 · 2015: 25 · 2014: 29 · 2013: 29 · 2012: 15
- FWCI
- 15.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- The Journal of Experimental Medicine (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by-nc-sa)
- Funders
- Ministry of Earth Sciences
- Universitair Medisch Centrum Groningen
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Blood disorders and treatments
- Keywords
- hematopoietic stem cells, aging, clonal analysis, HSC self-renewal, stromal co-culture, serial transplantation, cellular aging
- MeSH terms
- Animals, Antigens, Differentiation, Colony-Forming Units Assay, Hematopoietic Stem Cells, Mice, Transgenic, Transplantation, Homologous, Cellular Senescence, Hematopoietic Stem Cell Transplantation, Cell Proliferation, Mice
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