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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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BackgroundDebra-Mediated Ci Degradation Controls Tissue Homeostasis in Drosophila Adult Midgut
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BackgroundSignaling Pathways Regulating Hematopoietic Stem Cell and Progenitor Aging
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Self-citationOsteoblast Lineage Support of Hematopoiesis in Health and Disease
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“Aging leads to HSC-intrinsic changes, including DNA damage and altered metabolic and transcriptional activity that underlie a myeloid-biased skew and loss of self-renewal and regenerative capacity in both mice((123-125)) and humans.”
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“There are several examples where homeostatic regulation mechanisms do not substantially change with aging, such as red blood cell production during physiological and pathological changes [39], myeloid progenitor number and developmental potential [23, 40], proliferation and mobilization of stem cells in response to G-…”
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“For example, aged HSCs are more likely to differentiate towards the myeloid lineage at the expense of the lymphoid lineage [19].”
BackgroundThe Periostin/Integrin-αv Axis Regulates the Size of Hematopoietic Stem Cell Pool in the Fetal Liver
Biswas, A., Roy, I. M., Babu, P., Manesia, J. K., Schouteden, S., Vijayakurup, V., Anto, R. J., Huelsken, J., Lacy‐Hulbert, A., Verfaillie, C. M., et al. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.06.022 · Cited by 24
“These changes involve increased proliferation of HSCs, poorer engraftment potential, and differentiation skewed toward myelopoiesis at the expense of lymphopoiesis (Rossi et al., 2005).”
BackgroundDRAG in situ barcoding reveals an increased number of HSPCs contributing to myelopoiesis with age
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. (2023) · Nature Communications · doi:10.1038/s41467-023-37167-8 · Cited by 25
“…alsoshowed that aged HSPCs have increased expression of genes related to in fl ammation, cytokine stimulation, cycling, and DNA damage, in line with prior data 4,5,12,13 , as well as transcriptomic changes related to the regulation of protein ubiquitination and the electron transport chain (Fig.”
Concise Reviews: A Stem Cell Apostasy: A Tale of Four H Words
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Some hematopoietic stem cells are more equal than others
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“…or CD150low HSCs strikingly diminishes with aging, suggesting that the well documented aging-related compromise of lymphopoiesis (Sudo et al., 2000; Rossi et al., 2005) is not caused by loss of lymphoid potential by a homogeneous population of stem cells, but rather by expansion of HSC populations…”
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DNA-Damage-Induced Differentiation in Hematopoietic Stem Cells
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“In the murine HSC system, several studies have reported an increase in the absolute number of phenotypically defined HSCs, although elderly animals have a reduced repopulation potential when compared to younger organisms [38–42].”
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“With ageing, HSCs expand in number but increasingly adopt a myeloid-biased differentiation program 12,38,39 ; we recapitulated HSC expansion and CD150 high myeloid-biased HSC enrichment with age, which DFI did not reverse (Extended Data Fig.”
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“Frequency of the CD11A Subfraction of HSCs Increases with Age Although HSC function declines with age, the frequency of phenotypic HSCs increases (Rossi et al., 2005).”
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“the consequences of microenvironment modifications [32]; second, despite the expression of telomerase, which preserves the length of telomeres during cell division, the activated stem cells may reach replicative senescence, as a consequence of both intrinsic alterations [28] and epigenetic factors [1, 22, 26].”
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Phosphoproteomic profiling of mouse primary HSPCs reveals new regulators of HSPC mobilization
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Self-citationEpigenetic Changes as a Target in Aging Haematopoietic Stem Cells and Age-Related Malignancies
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Tracking hematopoietic stem cells and their progeny using whole-genome sequencing
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The tumor suppression theory of aging
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“regenerative capacity and skewed differentiation (Geiger et al., 2013; Rossi et al., 2005) with increased self-renewal (Signer and Morrison,”
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“Interestingly, two cytokines associated with inflammaging, TNF and IFN-γ, have been shown to downregulate CSF-1R expression (Rovida et al., 2001; Delneste et al., 2003) and circulating CSF-1 is also increased during aging (Suehiro et al., 1999; Larsson et al., 2015; Lira-Junior et al., 2017).”
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Self-citationGrowth hormone receptor signaling is dispensable for HSC function and aging
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“Together, our results show that exogenous rGh treatment differentially affects lineage potential of young and old HSCs, and induces a more balanced lineage output from aged HSCs. Genetic ablation reveals that Ghr is dispensable for”
BackgroundInfluentialSelf-citationEliciting the T cell fate with Notch
Sultana, D. A., Bell, J. J., Zlotoff, D. A., Obaldia, M. E. D., & Bhandoola, A. (2010) · Seminars in Immunology · doi:10.1016/j.smim.2010.04.011 · Cited by 24
“Indeed, the selectin/ligand pair P-selectin/ PSGL-1 have been demonstrated to play a role in thymic settling [24].”
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“It is well established that hematopoiesis changes with age (16, 17), leading to altered effector cell production and lineage potential (18).”
Cancer chemotherapy in the elderly patient.
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Is Age an Independent Risk Factor for Chemically Induced Acute Myelogenous Leukemia in Children?
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“However, recent evidence in experimental animals suggest that there are age-related differences in the expression of myeloid specific genes as well as in the ability of hematopoietic progenitor cells (HPC) to regenerate lymphoid versus myeloid progenitors (Rossi et al., 2005).”
BackgroundKaschutnig, P., Bogeska, R., Walter, D., Lier, A., Huntscha, S., & Milsom, M. D. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1068474 · Cited by 25
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BackgroundHow age affects human hematopoietic stem and progenitor cells and the strategies to mitigate aging
Li, X., Wang, J., Hu, L., & Cheng, T. (2025) · Experimental Hematology · doi:10.1016/j.exphem.2025.104711 · Cited by 25
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“We also detect a myeloid skewing phenotype, which is consistent with a HSPC aging phenotype (Liang et al., 2005; Rossi et al., 2005).”
ResultHepatic macrophage accumulation with aging: cause for concern?
Bloomer, S. A., & Moyer, E. D. (2021) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00286.2020 · Cited by 24
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“Aged HSCs exhibit impaired self-renewal and long-term reconstitution potential both in competitive and noncompetitive settings (14, 15), presumably due to the increased proliferative stress following HSC engraftment (16, 17).”
BackgroundTang, X. T., Wang, Z., Wang, J., Cui, S., Xu, R., & Wang, Y. (2023) · Stem Cell Research & Therapy · doi:10.1186/s13287-023-03316-5 · Cited by 24
“This may be because the proportion of HSCs in the BM of old mice is relatively high [38], but their function is defective, and they cannot maintain normal hematopoiesis [39].”
BackgroundA state-of-the-art review on the MicroRNAs roles in hematopoietic stem cell aging and longevity
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The multifaceted role of mitochondria in HSC fate decisions: energy and beyond
Filippi, M. (2023) · Experimental Hematology · doi:10.1016/j.exphem.2023.10.001 · Cited by 24
Regulation of asymmetric stem cell division: spindle orientation and the centrosome
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The effect of age on stem cell function and utility for therapy
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NAD+ augmentation with nicotinamide riboside improves lymphoid potential of Atm−/− and old mice HSCs
Zong, L., Tanaka-Yano, M., Park, B., Yanai, H., Turhan, F. T., Croteau, D. L., Tian, J., Fang, E. F., Bohr, V. A., & Beerman, I. (2021) · npj Aging and Mechanisms of Disease · doi:10.1038/s41514-021-00078-3 · Cited by 22
TNFAIP3 Plays a Role in Aging of the Hematopoietic System
Smith, M. A., Culver‐Cochran, A. E., Adelman, E. R., Rhyasen, G. W., Ma, A. I., Figueroa, M. E., & Starczynowski, D. T. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.536442 · Cited by 20
“During aging, HSCs increase in frequency, undergo myeloid-biased lineage priming and differentiation, and exhibit a functional decline in regeneration potential (9, 11, 12).”
BackgroundMegakaryocytes as the Regulator of the Hematopoietic Vascular Niche
Zhan, H., & Kaushansky, K. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.912060 · Cited by 23
Intersection of Inflammation and Senescence in the Aging Lung Stem Cell Niche
Allen, N. C., Reyes, N. S., Lee, J. Y., & Peng, T. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.932723 · Cited by 24
Orschell, C. M., Wu, T., & Patterson, A. M. (2022) · Current Stem Cell Reports · doi:10.1007/s40778-022-00214-z · Cited by 23
New insight into the causes, consequences, and correction of hematopoietic stem cell aging
Mansell, E., Lin, D. S. Y., Loughran, S. J., Milsom, M. D., & Trowbridge, J. J. (2023) · Experimental Hematology · doi:10.1016/j.exphem.2023.07.002 · Cited by 21
Long term human reconstitution and immune aging in NOD-Rag (−)-γ chain (−) mice
Harris, D. T., & Badowski, M. (2013) · Immunobiology · doi:10.1016/j.imbio.2013.08.013 · Cited by 22
Lnk deficiency partially mitigates hematopoietic stem cell aging
Bersenev, A., Rozenova, K., Balcerek, J., Jiang, J., Wu, C., & Tong, W. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00862.x · Cited by 24
“Notably, age-related changes in the HSC compartment correlate with organismal aging, which manifests as anemia, increased propensity for myeloproliferative neoplasms (MPNs), decreased immune function, and increased cancer incidence (Morrison et al., 1996; Sudo et al., 2000; Rossi et al., 2005; Chambers et al., 2007).”
BackgroundMethodResultInfluentialWeissman, I. L. (2016) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112003 · Cited by 24
Self-citationFunctional compensation between hematopoietic stem cell clones in vivo
Nguyen, L., Wang, Z., Chowdhury, A. Y., Chu, E., Eerdeng, J., Du, J., & Lu, R. (2018) · EMBO Reports · doi:10.15252/embr.201745702 · Cited by 22
“Functional compensation between HSCs, especially in the lymphoid lineages, may also take place during aging, as lymphopoietic deficiencies often develop in the elderly [7].”
Balogh, P., Adelman, E. R., Pluvinage, J. V., Capaldo, B. J., Freeman, K. C., Singh, S., Elagib, K. E., Nakamura, Y., Kurita, R., Sashida, G., et al. (2019) · Haematologica · doi:10.3324/haematol.2018.208918 · Cited by 21
“Epigenetic and transcriptomic analysis of aged HSC have also indicated that myeloid-skewing may manifest after similar changes.(6,7) Other aging-like phenotypes of RUNX3 deficiency include expansion of the LSK HSPC compartment, and increased HSPC mobilization in response to G-CSF.”
BackgroundSelf-citationJensen, K., Rother, M. B., Brusletto, B. S., Olstad, O. K., Aass, H. C. D., van Zelm, M. C., Kierulf, P., & Gautvik, K. M. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203462 · Cited by 22
“first manifested in hematopoietic stem cells (11, 12).”
BackgroundSekulovic, S., Gylfadottir, V., Vulto, I. M., Gasparetto, M., Even, Y., Brookes, C., Smith, C. A., Eaves, C. J., Lansdorp, P. M., Rossi, F. M. V., et al. (2011) · Blood · doi:10.1182/blood-2010-11-319632 · Cited by 23
Seach, N., Layton, D., Lim, J., Chidgey, A. P., & Boyd, R. L. (2007) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2007.07.001 · Cited by 22
Single-cell multi-scale footprinting reveals the modular organization of DNA regulatory elementsPreprint
Hu, Y., Ma, S., Kartha, V. K., Duarte, F. M., Horlbeck, M. A., Zhang, R., Shrestha, R., Labade, A. S., Kletzien, H., Meliki, A., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.28.533945 · Cited by 22
“In particular, HSCs have been shown to be compromised in function during aging, contributing to deficient pathogen-and vaccine-evoked immunity and heightened inflammatory responses 31– 33 .”
BackgroundSelf-citationKent, D. G., Dykstra, B. J., & Eaves, C. J. (2016) · Current Protocols in Stem Cell Biology · doi:10.1002/cpsc.10 · Cited by 21
Srinivasan, J., Vasudev, A., Shasha, C., Selden, H. J., Perez, E., LaFleur, B., Sinari, S. A., Krueger, A., Richie, E. R., & Ehrlich, L. I. R. (2023) · Aging Cell · doi:10.1111/acel.13870 · Cited by 23
Load and lock: the molecular mechanisms of B‐lymphocyte commitment
Zandi, S., Bryder, D., & Sigvardsson, M. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00950.x · Cited by 21
“Furthermore, Gfi-1 was shown regulated by the Znfinger transcription factor Ikaros, crucial for the normal development of B-lymphoid progenitor cells (43) and for the development of GMLPs ⁄ LMPPs (44).”
BackgroundResultInfluentialSelf-citationIyer, S., Brooks, R., Gumbleton, M., & Kerr, W. G. (2014) · Stem Cells and Development · doi:10.1089/scd.2014.0501 · Cited by 20
“However, consistent with aging, we did observe a decrease in MPP population [6] in both age-matched OSXCreSHIP and SHIP controls (Fig.”
ResultKing, A. M., Keating, P., Prabhu, A., Blomberg, B. B., & Riley, R. L. (2009) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.03.002 · Cited by 21
“However, it is also likely that intrinsic deficits in hematopoietic stem cell function may contribute to deficiencies in aged mice (Rossi et al., 2005; Guerrattaz et al., 2008).”
BackgroundHoming and Long-Term Engraftment of Long- and Short-Term Renewal Hematopoietic Stem Cells
Liu, L., Papa, E. F., Dooner, M. S., Machan, J. T., Johnson, K. W., Goldberg, L. R., Quesenberry, P. J., & Colvin, G. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031300 · Cited by 21
“This work has formed the basis for a detailed marrow stem/progenitor cell hierarchy [1–23] in which the most primitive stem cells differentiate into progressively more mature marrow cells with gains of specific function and loss of proliferative, renewal, and total differentiation potential.”
BackgroundImmunological aspects of age-related diseases
Isobe, K., Nishio, N., & Hasegawa, T. (2017) · World Journal of Biological Chemistry · doi:10.4331/wjbc.v8.i2.129 · Cited by 22
Rožman, P. J. (2018) · GeroScience · doi:10.1007/s11357-018-0027-x · Cited by 20
Novel Approaches to Target Mutant FLT3 Leukaemia
Müller, J. P., & Schmidt‐Arras, D. (2020) · Cancers · doi:10.3390/cancers12102806 · Cited by 21
“Loss of immune function and an increased incidence of myeloid leukaemia are two of the most clinically significant consequences of ageing of the haematopoietic system [60].”
BackgroundMesenchymal Stem Cell Therapy for Heart Disease
Gnecchi, M., & Cervio, E. (2012) · Humana Press eBooks · doi:10.1007/978-1-62703-200-1_13 · Cited by 21
Aging, hematopoiesis, and the myelodysplastic syndromes
Chung, S. S., & Park, C. Y. (2017) · Hematology · doi:10.1182/asheducation-2017.1.73 · Cited by 24
“In addition, immunophenotypically defined hematopoietic stem cells (HSCs) are increased in number, presumably to compensate for a concomitant decline in their output on a per-cell basis to maintain blood production.(3,4) The characterization of HSC cellular and transcriptomal changes during aging has revealed alterati…”
BackgroundChronic B Cell Deficiency from Birth Prevents Age-Related Alterations in the B Lineage
Zohar, K., Averbuch, D., Shahaf, G. L., Zisman‐Rozen, S., Golan, K., Itkin, T., Lapidot, T., Mehr, R., & Melamed, D. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100999 · Cited by 21
“The loss of B cell production potential with age is thought to result from intrinsic defects in gene expression and dysregulated epigenetic control in LTR-HSCs (10, 11, 46).”
BackgroundInfluentialNogalska, A., Eerdeng, J., Akre, S., Vergel-Rodriguez, M., Lee, Y., Bramlett, C. S., Chowdhury, A. Y., Wang, B., Cess, C. G., Finley, S. D., et al. (2024) · Cellular and Molecular Immunology · doi:10.1038/s41423-024-01225-y · Cited by 20
“This aging phenotype is highly relevant to disease genesis, as elderly individuals often suffer from increased myeloid leukemia [3, 6, 7] and immune de fi ciencies [3, 6, 8, 9].”
Thymic Engraftment by in vitro-Derived Progenitor T Cells in Young and Aged Mice
Singh, J., Mohtashami, M., Anderson, G., & Zúñiga‐Pflücker, J. C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01850 · Cited by 21
Extracellular Vesicles and Hematopoietic Stem Cell Aging
Goldberg, L. R. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314643 · Cited by 20
“Although likely to evolve as we gain more insight into EV biogenesis and function, EVs are currently categorized broadly based on size and biogenesis into groups: (1) exosomes (small EVs) that range from 30 to 150 nm and arise from the endosomal pathway; (2) microvesicles (larger EVs, medium/large EVs, also called mic…”
Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice
Donham, C., Chicana, B. J., Robling, A. G., Mohamed, A. H., Elizaldi, S. R., Chi, M., Freeman, B., Millan, A. J., Murugesh, D. K., Hum, N. R., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179111 · Cited by 22
“This general decline in HSC function includes a reduction in long-term repopulating potential, homing, and engraftment after transplantation [19], a decrease in lymphopoiesis, and increase in myelopoiesis [20,21], as well as an increase in the total number of LT-HSCs [22].”
BackgroundSingh, A., Chia, J. J., Rao, D. S., & Hoffmann, A. (2025) · Blood · doi:10.1182/blood.2024025598 · Cited by 21
A Resource for Discovering Specific and Universal Biomarkers for Distributed Stem Cells
Noh, M., Smith, J. L., Huh, Y. H., & Sherley, J. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022077 · Cited by 20
“Highly-enriched LT-HSCs isolated for young animals at 2–3 months of age or old animals at 22–24 months of age were not significantly different for degree of asymmetric self-renewal character (GSE4332).”
BackgroundAging, B lymphopoiesis, and patterns of leukemogenesis
Signer, R. A. J., Montecino‐Rodriguez, E., & Dorshkind, K. A. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.11.010 · Cited by 20
“Interestingly, gene profiling of young and old HSC indicate that the latter do not exhibit changes typically associated with aging in non-blood cells (Rossi et al., 2005).”
BackgroundWang, C., Oshima, M., Sashida, G., Tomioka, T., Hasegawa, N., Mochizuki‐Kashio, M., Nakajima‐Takagi, Y., Kusunoki, Y., Kyoizumi, S., Imai, K., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0132041 · Cited by 22
“Because impaired reconstituting capacity, myeloid-biased differentiation and inefficient production of B cells are hallmarks of aged HSCs [7], [10], [24], these data indicate that non-lethal doses of radiation accelerate part of the aging phenotypes of human HSPCs in humanized mice.”
BackgroundStem cell ageing: does it happen and can we intervene?
Bellantuono, I., & Keith, W. N. (2007) · Expert Reviews in Molecular Medicine · doi:10.1017/s146239940700049x · Cited by 21
Arai, F., Stumpf, P. S., Ikushima, Y. M., Hosokawa, K., Roch, A., Lutolf, M. P., Suda, T., & MacArthur, B. D. (2020) · Cell Systems · doi:10.1016/j.cels.2020.11.004 · Cited by 19
Formula G1: Cell cycle in the driver's seat of stem cell fate determination
Julian, L. M., Carpenedo, R. L., Rothberg, J. L. M., & Stanford, W. L. (2016) · BioEssays · doi:10.1002/bies.201500187 · Cited by 19
“While fetal HSCs produce a balanced population of committed hematopoietic lineages needed to sustain hematopoiesis, aged HSCs show a reduced entry into the cell cycle and lineage bias, with an elevated myeloid/lymphoid ratio [64].”
BackgroundBonora, B. M., Palano, M. T., Testa, G., Fadini, G. P., Sangalli, E., Madotto, F., Persico, G., Casciaro, F., Vono, R., Colpani, O., et al. (2022) · Aging Cell · doi:10.1111/acel.13545 · Cited by 19
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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