The DOI matches its Crossref record; 46 of the 47 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Citations
Cites
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219
Stem cells, cancer, and cancer stem cells
Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001) · Nature · doi:10.1038/35102167 · Cited by 9,738
Self-citationModel-based analysis of oligonucleotide arrays: Expression index computation and outlier detection.
Li, C., & Wong, W. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.31 · Cited by 3,133
Purification and Characterization of Mouse Hematopoietic Stem Cells
Spangrude, G. J., Heimfeld, S., & Weissman, I. L. (1988) · Science · doi:10.1126/science.2898810 · Cited by 2,908
Self-citationIsolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.
Goodell, M. A., Brose, K., Paradis, G. A., Conner, A. N., & Mulligan, R. C. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.4.1797 · Cited by 2,902
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
Akashi, K., Traver, D., Miyamoto, T., & Weissman, I. L. (2000) · Nature · doi:10.1038/35004599 · Cited by 2,617
Self-citationIdentification of Clonogenic Common Lymphoid Progenitors in Mouse Bone Marrow
Kondo, M., Weissman, I. L., & Akashi, K. (1997) · Cell · doi:10.1016/s0092-8674(00)80453-5 · Cited by 2,253
Self-citationLong-Term Lymphohematopoietic Reconstitution by a Single CD34-Low/Negative Hematopoietic Stem Cell
Osawa, M., Hanada, K., Hamada, H., & Nakauchi, H. (1996) · Science · doi:10.1126/science.273.5272.242 · Cited by 2,141
Gene regulation and DNA damage in the ageing human brain
Lu, T., Pan, Y., Kao, S.-Y., Li, C., Kohane, I., Chan, J., & Yankner, B. A. (2004) · Nature · doi:10.1038/nature02661 · Cited by 1,874
Research works printed but not linked: 1
- Yang, L., Bryder, D., Adolfsson, J., Nygren, J., Mansson, R., Sigvardsson, M. & Jacobsen, S. E. (2004) Blood 105, 2717-2723.15572596
Cited by
Sorted by citations
Items 401–500 of 999
Konturek-Cieśla, A., Dhapola, P., Zhang, Q., Säwén, P., Wan, H., Karlsson, G., & Bryder, D. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112304 · Cited by 44
Self-citationClonal haematopoiesis, ageing and kidney disease
Vlasschaert, C., Lanktree, M. B., Rauh, M. J., Kelly, T. N., & Natarajan, P. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00778-x · Cited by 42
Zhang, S., & Bhandoola, A. (2013) · Current topics in microbiology and immunology · doi:10.1007/82_2013_324 · Cited by 45
The epigenetic basis of hematopoietic stem cell aging
Kramer, A. C., & Challen, G. A. (2016) · Seminars in Hematology · doi:10.1053/j.seminhematol.2016.10.006 · Cited by 44
Regulation of the hematopoietic stem cell lifecycle by the endothelial niche
Ramalingam, P., Poulos, M. G., & Butler, J. M. (2017) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000350 · Cited by 45
Sheshadri, A., Chemaly, R. F., Alousi, A. M., Shah, P., Rondón, G., Bashoura, L., Kmeid, J., Azzi, J. M., Blanco, D., Kaous, M., et al. (2018) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2018.11.022 · Cited by 42
“Advanced age is a well-known marker of adverse outcomes after viral LRI (55) and may be explained in part by the shift from lymphoid to myeloid cell proliferation (56), impaired B- and T-cell lymphopoiesis (57, 58), and impaired T-cell co-stimulation (59).”
BackgroundCairney, C. J., Sanguinetti, G., Ranghini, E. J., Chantry, A., Nostro, M. C., Bhattacharyya, A., Svendsen, C. N., Keith, W. N., & Bellantuono, I. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.01.015 · Cited by 43
Foxo3a is essential for maintenance of the hematopoietic stem cell pool.
Miyamoto, K., Araki, K. Y., Naka, K., Arai, F., Takubo, K., Yamazaki, S., Matsuoka, S., Miyamoto, T., Ito, K., Ohmura, M., et al. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.02.001 · Cited by 41
Xiao, N., Jani, K., Morgan, K. J., Okabe, R. O., Cullen, D. E., Jesneck, J. L., & Raffel, G. D. (2012) · Blood · doi:10.1182/blood-2012-01-403089 · Cited by 44
Unraveling the complex regulation of stem cells: implications for aging and cancer
Oakley, E. J., & Zant, G. E. V. (2007) · Leukemia · doi:10.1038/sj.leu.2404530 · Cited by 42
Quantitative stem cell biology: computational studies in the hematopoietic system
Roeder, I. (2006) · Current Opinion in Hematology · doi:10.1097/01.moh.0000231418.08031.48 · Cited by 41
Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function
Kosan, C., & Godmann, M. (2015) · Stem Cells International · doi:10.1155/2016/5178965 · Cited by 47
“Aging of the hematopoietic system is associated with several changes like reduced lymphocyte counts and antibody diversity, autoimmunity, altered regeneration potential, and finally diseases like leukemia [141–143].”
Myelodysplastic syndrome: An inability to appropriately respond to damaged DNA?
Zhou, T., Hasty, P., Walter, C. A., Bishop, A. J. R., Scott, L. M., & Rebel, V. I. (2013) · Experimental Hematology · doi:10.1016/j.exphem.2013.04.008 · Cited by 39
Watanuki, S., Kobayashi, H., Sugiura, Y., Yamamoto, M., Karigane, D., Shiroshita, K., Sorimachi, Y., Morikawa, T., Fujita, S., Shide, K., et al. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.04.023 · Cited by 40
Regulation and Function of Skeletal Muscle Stem CellsPreprint
Cerletti, M., Shadrach, J. L., Jurga, S., Sherwood, R. I., & Wagers, A. J. (2008) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2008.73.054 · Cited by 40
Self-citationEpigenetic Regulation of Aging and its Rejuvenation
An, Y., Wang, Q., Gao, K., Zhang, C., Ouyang, Y., Li, R., Zhou, M., Wu, T., Zhou, L., Xie, Z., et al. (2025) · MedComm · doi:10.1002/mco2.70369 · Cited by 47
Transcription factor‐mediated reprogramming toward hematopoietic stem cells
Ebina, W., & Rossi, D. J. (2015) · The EMBO Journal · doi:10.15252/embj.201490804 · Cited by 41
“Since it is unclear whether HSCs could ever be expanded to the same extent as iPSCs while avoiding functional decline as seen with aging (Rossi et al , 2005; Beerman et al , 2013; Beerman & Rossi, 2014; Sun et al , 2014a), an ideal solution would entail near deterministic induction of HSCs from…”
Self-citationAl-Chami, E., Tormo, A. J., Pasquin, S., Kanjarawi, R., Ziouani, S., & Rafei, M. (2016) · Aging Cell · doi:10.1111/acel.12440 · Cited by 42
“Such alterations are elemental to thymopoiesis as the STHSC and MPP fractions both lie upstream of CLP and contribute to lymphoid reconstitution (Rossi et al., 2005).”
BackgroundResultInfluentialAlcam Regulates Long-Term Hematopoietic Stem Cell Engraftment and Self-Renewal
Jeannet, R., Cai, Q., Liu, H., Vu, H., & Kuo, Y. (2012) · Stem Cells · doi:10.1002/stem.1309 · Cited by 39
Lima, M. J. G. D., & Giralt, S. A. (2006) · Seminars in Hematology · doi:10.1053/j.seminhematol.2006.01.004 · Cited by 39
Allorecognition polymorphism versus parasitic stem cells
DeTomaso, A. (2006) · Trends in Genetics · doi:10.1016/j.tig.2006.07.001 · Cited by 39
Haematopoietic stem and progenitor cells in rheumatoid arthritis.
Colmegna, I., & Weyand, C. M. (2011) · Rheumatology · doi:10.1093/rheumatology/keq298 · Cited by 37
Cellular plasticity of the bone marrow niche promotes hematopoietic stem cell regeneration
Hirakawa, H., Gao, L., Tavakol, D. N., Vunjak‐Novakovic, G., & Ding, L. (2023) · Nature Genetics · doi:10.1038/s41588-023-01528-2 · Cited by 41
Stromal pleiotrophin regulates repopulation behavior of hematopoietic stem cells
Istvánffy, R., Kröger, M., Eckl, C., Gitzelmann, S., Vilne, B., Bock, F., Graf, S., Schiemann, M., Keller, U. B., Peschel, C., et al. (2011) · Blood · doi:10.1182/blood-2010-05-287235 · Cited by 44
Concise Review: Hematopoietic Stem Cell Aging and the Prospects for Rejuvenation
Wahlestedt, M., Pronk, C. J., & Bryder, D. (2014) · Stem Cells Translational Medicine · doi:10.5966/sctm.2014-0132 · Cited by 38
Self-citationMosteo, L., Storer, J. A., Batta, K., Searle, E. J., Duarte, D., & Wiseman, D. H. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.635189 · Cited by 44
“Indeed, mathematical models suggest that non-cell autonomous features rather than somatic mutations predominantly drive clonal expansion of mutated stem cells (Rozhok et al., 2014).”
BackgroundKhong, D., Dudakov, J. A., Hammett, M. V., Jurblum, M. I., Khong, S. M. L., Goldberg, G. L., Ueno, T., Spyroglou, L., Young, L. F., van den Brink, M. R. M., et al. (2015) · Stem Cell Reports · doi:10.1016/j.stemcr.2015.01.018 · Cited by 40
“Consistent with the marked shift in lineage differentiation potential of HSCs with age, previous studies have found considerable gene usage skewing in HSCs from old mice away from lymphoid-associated and toward myeloid-associated genes (Rossi et al., 2005).”
ResultAdult Cardiac Stem Cell Aging: A Reversible Stochastic Phenomenon?
Cianflone, E., Torella, M., Chimenti, C., Angelis, A. D., Beltrami, A. P., Urbanek, K., Rota, M., & Torella, D. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/5813147 · Cited by 40
MacDonald, J. A., Takai, Y., Ishihara, O., Seki, H., Woods, D. C., & Tilly, J. L. (2019) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.12.015 · Cited by 38
Epigenetic Clock: Just a Convenient Marker or an Active Driver of Aging?
Ashapkin, V. V., Kutueva, L. I., & Vanyushin, B. F. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-25650-0_10 · Cited by 41
Zanetti, C., Kumar, R., Ender, J., Godavarthy, P. S., Hartmann, M., Hey, J., Breuer, K., Weissenberger, E. S., Minciacchi, V. R., Karantanou, C., et al. (2021) · Blood · doi:10.1182/blood.2021011557 · Cited by 37
Khatri, R., Krishnan, S., Roy, S., Chattopadhyay, S., Kumar, V., & Mukhopadhyay, A. (2016) · Stem Cells and Development · doi:10.1089/scd.2015.0391 · Cited by 37
“The reasons for stem cells aging are unraveling, however, collective evidences suggest that lineage potential, homing efficiency, change of transcriptional activity, genomic integrity, and cellular metabolism in aging HSCs are intrinsically controlled [17,32].”
BackgroundMobilization‐based transplantation of young‐donor hematopoietic stem cells extends lifespan in mice
Guderyon, M. J., Chen, C., Bhattacharjee, A., Ge, G., Fernandez, R. A., Gelfond, J., Gorena, K. M., Cheng, C. J. A., Li, Y., Nelson, J. F., et al. (2020) · Aging Cell · doi:10.1111/acel.13110 · Cited by 37
“Remarkably, white blood cell populations (WBCs) derived from young-donor HSCs within aged recipients (GFP+) retained their youthful phenotypic distribution (Figure 4b; Table S4; Rossi et al., 2005).”
BackgroundZhang, X., Baht, G. S., Rong, H., Chen, Y., Molitoris, K. H., Miller, S., & Kraus, V. B. (2022) · Aging Cell · doi:10.1111/acel.13651 · Cited by 36
“Taken together, these results suggest an immunosenescence phenotype in aged mice that may result from a deficiency in hematopoietic stem cell differentiation into terminal lymphoid cells (Rossi et al., 2005).”
BackgroundResultSong, Z., Zhang, J., Ju, Z., & Rudolph, K. L. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00802.x · Cited by 36
“young mice (Rossi et al., 2005; Chambers et al., 2007) and have led to the concept that HSC aging can be induced by cell intrinsic factors.”
BackgroundForsberg, E. C., Bhattacharya, D., & Weissman, I. L. (2006) · Stem Cell Reviews and Reports · doi:10.1007/s12015-006-0005-z · Cited by 36
Self-citationHuman stem cell aging: do mitochondrial DNA mutations have a causal role?
Baines, H. L., Turnbull, D. M., & Greaves, L. C. (2013) · Aging Cell · doi:10.1111/acel.12199 · Cited by 35
“However, in the majority of cases, stem cells endure alterations in their normal fate and function of their progeny due to disturbances in differentiation, as seen in hematopoietic stem cells (HSCs) (Rossi et al., 2005).”
BackgroundAt the stem of youth and health
Beltrami, A. P., Cesselli, D., & Beltrami, C. A. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.10.005 · Cited by 36
“For this reason, pathological and patho-physiological conditions characterized by altered tissue homeostasis and impaired regenerative capacity can be viewed as a consequence of the reduction in stem cell number and/or function (Sharpless & DePinho, 2007; Rossi et al., 2008).”
BackgroundAging of the hematopoietic stem cells niche
Nakamura‐Ishizu, A., & Suda, T. (2014) · International Journal of Hematology · doi:10.1007/s12185-014-1641-8 · Cited by 36
Cozzarini, C., Chiorda, B. N., Sini, C., Fiorino, C., Briganti, A., Montorsi, F., & Muzio, N. G. D. (2016) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2016.01.022 · Cited by 35
van Beek, A. A., Hugenholtz, F., Meijer, B., Sovran, B., Perdijk, O., Vermeij, W. P., Brandt, R. M. C., Barnhoorn, S., Hoeijmakers, J. H. J., de Vos, P., et al. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.1hi0216-062rr · Cited by 36
“With age, hematopoietic stem cells acquire defects [1, 2] and do not efficiently generate lymphoid cells, whereas relatively more myeloid cells are generated [3, 4].”
BackgroundMyeloid-Derived Suppressor Cells at the Intersection of Inflammaging and Bone Fragility
Kirkwood, K. L., Zhang, L., Thiyagarajan, R., Seldeen, K. L., & Troen, B. R. (2018) · Immunological Investigations · doi:10.1080/08820139.2018.1552360 · Cited by 36
“This shift has been correlated with increased expression of myeloid lineage genes and downregulation of those specifying a lymphoid lineage fate (Pang et al., 2011; Rossi et al., 2005).”
BackgroundThe developmental stage of the hematopoietic niche regulates lineage in MLL-rearranged leukemia
Rowe, R. G., da Rocha, E. L., Sousa, P., Missios, P., Morse, M. A., Marion, W., Yermalovich, A. V., Barragan, J., Mathieu, R., Jha, D. K., et al. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20181765 · Cited by 34
Patterson, A. M., Vemula, S., Plett, P. A., Sampson, C. H., Chua, H. L., Fisher, A., Wu, T., Sellamuthu, R., Feng, H., Katz, B. P., et al. (2022) · Radiation Research · doi:10.1667/rade-22-00071.1 · Cited by 37
“Blood production becomes increasingly myeloid-biased with age (16, 18).”
BackgroundTaz protects hematopoietic stem cells from an aging-dependent decrease in PU.1 activity
Kim, K. M., Mura-Mészáros, A., Tollot, M., Krishnan, M. S., Gründl, M., Neubert, L., Groth, M., Rodriguez-Fraticelli, A., Svendsen, A. F., Campaner, S., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32970-1 · Cited by 37
The Biology of Aging and Lymphoma: a Complex Interplay
Sarkozy, C., Salles, G. A., & Falandry, C. (2015) · Current Oncology Reports · doi:10.1007/s11912-015-0457-x · Cited by 36
Immunosenescence in renal transplantation
Seyda, M., Quante, M., Uehara, H., Slegtenhorst, B. R., Elkhal, A., & Tullius, S. G. (2015) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0000000000000210 · Cited by 35
Prall, W. C., Czibere, A. G., Jäger, M., Spentzos, D., Libermann, T. A., Gattermann, N., Haas, R. R., & Aivado, M. A. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.06.008 · Cited by 35
Dawar, S., Shahrin, N. H., Sladojevic, N., D'Andrea, R. J., Dorstyn, L., Hiwase, D. K., & Kumar, S. (2016) · Cell Death & Disease · doi:10.1038/cddis.2016.406 · Cited by 30
“…even though the regenerative capacity of individual stem cells is reduced under stress (i.e., serial transplantation) compared with young HSCs. 29,30 Normally, the danger caused by mutagenic accumulation in ageing HSC is prevented by the activity of tumour suppressor proteins that sense…”
Extreme disruption of heterochromatin is required for accelerated hematopoietic aging
Keenan, C. R., Iannarella, N., Naselli, G., Bediaga, N. G., Johanson, T. M., Harrison, L. C., & Allan, R. S. (2020) · Blood · doi:10.1182/blood.2019002990 · Cited by 34
Bruserud, Ø., Vo, A. K., & Reikvam, H. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11030706 · Cited by 37
“Transplanted young hematopoietic stem cells engraft at a lower efficiency when transplanted to aged compared with young recipients [15,84].”
BackgroundTeissier, T., Temkin, V., Pollak, R. D., & Cox, L. S. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.812157 · Cited by 35
Adaptive immunity and atherosclerosis: aging at its crossroads
Snijckers, R., & Foks, A. C. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1350471 · Cited by 40
PLZF mutation alters mouse hematopoietic stem cell function and cell cycle progression
Vincent‐Fabert, C., Platet, N., Vandevelde, A., Poplineau, M., Koubi, M., Finetti, P., Tibéri, G., Imbert, A., Bertucci, F., & Duprez, E. (2016) · Blood · doi:10.1182/blood-2015-09-666974 · Cited by 35
“Aging HSCs have a reduction in their regenerative capacity and support decreased lymphoid lineage output together with increasedmyeloid output.(2,3) Surprisingly, the number of phenotypically definedHSCs increases with age; although it has long been known that aging has a major impact on the frequency and cell cycle k…”
BackgroundUpdates on Old and Weary Haematopoiesis
Konieczny, J., & Arranz, L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092567 · Cited by 34
“In contrast, myelopoiesis was reported to be relatively unaffected by ageing, as numbers of common myeloid progenitors and their progeny remain unchanged or increased in old mice [16,17].”
BackgroundCD34+ Stem Cells: Promising Roles in Cardiac Repair and Regeneration
Marvasti, T. B., Alibhai, F. J., Weisel, R. D., & Li, R. (2019) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2019.05.037 · Cited by 35
Cardin, S., Bilodeau, M., Roussy, M., Aubert, L., Milan, T., Jouan, L., Rouette, A., Laramée, L., Gendron, P., Duchaine, J., et al. (2019) · Blood Advances · doi:10.1182/bloodadvances.2019030981 · Cited by 34
“SELP, expressed in a subset of AMKL genetic subtypes, encodes the receptor P-selectin translocated at the cell surface of stimulated platelets and endothelial cells, and also expressed on megakaryocytes and aged murine hematopoietic stem cells.(48,49) Overall, the surface biomarkers upregulated in AMKL, as compared wi…”
BackgroundSchwab, J. D., Ikonomi, N., Werle, S. D., Weidner, F. M., Geiger, H., & Kestler, H. A. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.09.012 · Cited by 37
Sun, L., Brown, R. E., Chen, S., Zhuge, Q., & Su, D. (2012) · Aging · doi:10.18632/aging.100487 · Cited by 36
“This is in part due to the inadequate understanding of the divergent downregulated lymphoid and up-regulated myeloid gene expression profile in aged BM progenitors [20], and the myeloid-biased cellular differentiation of aged BM progenitors [10, 12], despite the argument that these may arise from the loss or expansion…”
BackgroundMitchell, K., & Steidl, U. G. (2019) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a036251 · Cited by 37
“This is accompanied by myeloid skewing, specifically demonstrated by increased myeloid repopulation potential in HSC transplantation experiments from young versus old mice and young versus old human BM specimens (Rossi et al. 2005; Rundberg Nilsson et al. 2016; Yamamoto et al. 2018).”
BackgroundLutzmann, M., Bernex, F., de Jesus, C. D. C., Hodroj, D., Marty, C., Plo, I., Vainchenker, W., Tosolini, M., Forichon, L., Bret, C., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.07.095 · Cited by 33
“This is an open access article under the CC BY-N mice (Sudo et al., 2000; Rossi et al., 2005).”
BackgroundAging and Clonal Behavior of Hematopoietic Stem Cells
Yamashita, M., & Iwama, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23041948 · Cited by 36
Stem Cell Ageing and Apoptosis
Fulle, S., Centurione, L., Mancinelli, R., Sancilio, S., Manzoli, F. A., & Pietro, R. D. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212799859657 · Cited by 33
“With regard to HSCs, the impact of ageing has been evaluated through a number of different assays [116, 117] that often lead to conflicting results, partly caused by differences in mouse strains.”
BackgroundCell intrinsic and extrinsic mechanisms of stem cell aging depend on telomere status
Song, Z., Ju, Z., & Rudolph, K. L. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2008.06.009 · Cited by 34
“Reduced expression of genes regulating lymphoid differentiation in HSCs from old compared to young mice (Rossi et al. 2005) Cell extrinsic: Efficient thymopoiesis of transplanted ‘young’ thymus in ‘old’ recipients indicating that aging of the thymic niche contributes to declining function (Mackall and Gress, 1997) Res…”
BackgroundInfluentialInnate Regeneration in the Aging Heart: Healing From Within
Anversa, P., & Leri, A. (2013) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2013.04.001 · Cited by 32
Data normalization considerations for digital tumor dissection
Newman, A. M., Gentles, A. J., Liu, C. L., Diehn, M., & Alizadeh, A. A. (2017) · Genome biology · doi:10.1186/s13059-017-1257-4 · Cited by 30
“Separately, age-related lymphomyeloid lineage skewing of hematopoiesis [13] would be expected to further confound this assumption.”
BackgroundHematopoiesis during Ontogenesis, Adult Life, and Aging
Belyavsky, A. V., Петинати, Н. А., & Дризе, Н. И. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179231 · Cited by 37
Are epidermal stem cells unique with respect to aging?
Racila, D. M., & Bickenbach, J. R. (2009) · Aging · doi:10.18632/aging.100082 · Cited by 32
“A further point to consider is do organisms proceed through the aging process because they gradually lose their stem cells as they age or because their stem cells gradually change their function? Evidence from intestinal and hematopoietic stem cells suggest that both may happen: the number of stem cells decreases and…”
BackgroundShima, T., Miyamoto, T., Kikushige, Y., Mori, Y., Kamezaki, K., Takase, K., Henzan, H., Numata, A., Ito, Y., Takenaka, K., et al. (2012) · Blood · doi:10.1182/blood-2012-02-409607 · Cited by 31
Regulation of stem cell aging by SIRT1 – Linking metabolic signaling to epigenetic modifications
An, Y., & Dang, W. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.03.031 · Cited by 32
“This results in a larger number of HSCs with much reduced clonal complexity in old mice than M AN US CR IP T AC CE PT ED in young mice (Rossi et al., 2005).”
BackgroundFeeding the fire: the role of defective bone marrow function in exacerbating thymic involution
Dudakov, J. A., Khong, D., Boyd, R. L., & Chidgey, A. P. (2010) · Trends in Immunology · doi:10.1016/j.it.2010.02.002 · Cited by 31
Bone Marrow Support of the Heart in Pressure Overload Is Lost with Aging
Sopko, N. A., Turturice, B. A., Becker, M. E., Brown, C. R., Dong, F., Popović, Z., & Penn, M. S. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015187 · Cited by 31
“Since aging affects the expression of genes involved in transmembrane, Gprotein-coupled receptor, and protein tyrosine phosphatase signaling activity [27], we measured the migration potential of lineage depleted young and old BM cells in response to MCP-3 and SDF-1; these two chemokines have been shown to be highly re…”
BackgroundCav-1 deletion impaired hematopoietic stem cell function
Bai, L., Shi, G., Zhang, L., Guan, F., Ma, Y., Li, Q., Cong, Y.-S., & Zhang, L. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.105 · Cited by 31
“in the BM and PB, which was similar to what was observed during aging of WT mice.(8,22)”
BackgroundResultMolecular landscapes of human hematopoietic stem cells in health and leukemia
Vedi, A., Santoro, A., Dunant, C. F., Dick, J. E., & Laurenti, E. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12981 · Cited by 32
Identification of early myeloid progenitors as immunosuppressive cells
Pu, S., Qin, B., He, H., Zhan, J., Wu, Q., Zhang, X., Yang, L., Qu, C., & Zhou, Z. (2016) · Scientific Reports · doi:10.1038/srep23115 · Cited by 31
Hisamatsu, D., Ohno‐Oishi, M., Nakamura, S., Mabuchi, Y., & Naka-Kaneda, H. (2016) · Aging · doi:10.18632/aging.100982 · Cited by 31
“…homeostasis, e.g., dysregulation of hematopoiesis due to a decline in the lymphopoietic potential of hematopoietic stem/progenitor cells (HSCs) [10, 11]; reduced muscle repair capacity due to diminished activity of skeletal muscle satellite cells [12-14]; and loss of multipotency (i.e., the…”
Sharma, S., & Bhonde, R. R. (2020) · Genomics · doi:10.1016/j.ygeno.2020.04.022 · Cited by 32
Mitigating oxygen stress enhances aged mouse hematopoietic stem cell numbers and function
Capitano, M. L., Mohamad, S., Cooper, S. H., Guo, B., Huang, X., Gunawan, A. M., Sampson, C. H., Ropa, J. P., Srour, E. F., Orschell, C. M., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci140177 · Cited by 30
“At 6 months, ambient air–acclimated young donor cells showed greater engraftment of peripheral blood (PB) (Figure 2B) and BM (Figure 2C) than did ambient air–collected cells from the old mice, consistent with other reports in the literature (1, 5, 28, 29).”
ResultEpigenetic Clock and Circadian Rhythms in Stem Cell Aging and Rejuvenation
Samoilova, E. M., Викторович, Б. В., Ekusheva, E. V., Zhang, C., Troitskiy, A. V., & Baklaushev, V. P. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11111050 · Cited by 32
“Another defining characteristic of HSC aging is a shift in the profile of their differentiation towards the myeloid row due to a decrease in the lymphoid row [102,105].”
BackgroundCdc42 and aging of hematopoietic stem cells
Geiger, H., & Zheng, Y. (2013) · Current Opinion in Hematology · doi:10.1097/moh.0b013e3283615aba · Cited by 32
“Aged HSCs exhibit distinct whole genome expression signatures [20,29] and increased double-strand breaks as detected by increased levels of gammaH2AX Geiger and Zheng Page 2”
Sirtuins in Hematological Aging and Malignancy
Roth, M., Wang, Z., & Chen, W. (2013) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.2013010187 · Cited by 31
Aging Impairs Long-Term Hematopoietic Regeneration after Autologous Stem Cell Transplantation
Woolthuis, C. M., Mariani, N., Verkaik‐Schakel, R. N., Brouwers-Vos, A. Z., Schuringa, J. J., Vellenga, E., de Wolf, J. T. M., & Huls, G. A. (2014) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2014.03.001 · Cited by 34
Reducing functionally defective old HSCs alleviates aging-related phenotypes in old recipient mice
Wang, Y., Zhang, W., Zhang, C., Van, H. Q. T., Seino, T., & Zhang, Y. (2025) · Cell Research · doi:10.1038/s41422-024-01057-5 · Cited by 34
Conboy (2008) · StemBook · doi:10.3824/stembook.1.11.1 · Cited by 32
“…LT-HSCs into young and old animals revealed that even in the aged bone marrow microniche, young HSCs produced B-cells at proper levels and thus scarce B-lymphopoiesis seems to be intrinsic to HSC aging and not due to the aging bone marrow microenvironment (Rossi et al., 2005; Rossi et al., 2007).”
BackgroundResultInfluentialFate of Hematopoiesis During Aging. What Do We Really Know, and What are its Implications?
Broxmeyer, H. E., Liu, Y., Kapur, R., Orschell, C. M., Aljoufi, A., Ropa, J. P., Trinh, T. L. P., Burns, S. S., & Capitano, M. L. (2020) · Stem Cell Reviews and Reports · doi:10.1007/s12015-020-10065-y · Cited by 30
Maimets, M., Bron, R., de Haan, G., van Os, R. P., & Coppes, R. P. (2015) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2015.06.022 · Cited by 33
“Similar observations have been made in long-term HSCs [20] and skeletal muscle [21].”
ResultFukuda, S., Hoggatt, J., Singh, P., Abe, M., Speth, J. M., Hu, P., Conway, E. M., Nucifora, G., Yamaguchi, S., & Pelus, L. M. (2014) · Leukemia · doi:10.1038/leu.2014.183 · Cited by 30
“gov/geo) showed that the Survivin signal was similarly expressed in mouse bone marrow Flt3 (CD135) neg CD34 neg KSL cells highly enriched for primitive HSC (25) (Figure 1B).”
BackgroundRozhok, A. I., Salstrom, J. L., & DeGregori, J. V. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1509333113 · Cited by 27
Davies, J. S., Thompson, H. L., Pulko, V., Padilla‐Torres, J., & Nikolich‐Žugich, J. (2017) · The Journals of Gerontology Series A · doi:10.1093/gerona/glx102 · Cited by 30
Implications of Epigenetic Variability within a Cell Population for “Cell Type” Classification
Tabansky, I., Stern, J. N. H., & Pfaff, D. W. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00342 · Cited by 30
“…variation already found in many kinds of cells, Frontiers in Behavioral Neuroscience | www.frontiersin.org 5 December 2015 | Volume 9 | Article 342 including neurons (Rahemtulla et al., 1991; Lu et al., 1997; Rossi et al., 2005; Beerman et al., 2010; Blanpain and Fuchs, 2014; Marder et al., 2015).”
InfluentialAn aging bone marrow exacerbates lung fibrosis by fueling profibrotic macrophage persistence
Farhat, A., Radhouani, M., Deckert, F., Zahalka, S., Pimenov, L., Fokina, A., Hakobyan, A., Oberndorfer, F., Brösamlen, J., Hladik, A., et al. (2025) · Science Immunology · doi:10.1126/sciimmunol.adk5041 · Cited by 35
Pantic, I. V., Pantic, S., & Paunović-Pantić, J. (2012) · Microscopy and Microanalysis · doi:10.1017/s1431927612001377 · Cited by 29
“…to increased expression of myeloid genes ~genes responsible for specifying myeloid fate of the cell! and decreased expression of lymphoid genes ~Rossi et al., 2005!. Chambers et al. ~2007! indicated that aged HSCs exhibit epigenetic dysregulation with lowered transcriptional regulation in…”
BackgroundPotential and pitfalls of stem cell therapy in old age
Piccin, D., & Morshead, C. M. (2010) · Disease Models & Mechanisms · doi:10.1242/dmm.003137 · Cited by 29
“, 2005) and, more recently, the role of DNA damage and telomere shortening in this process was determined using transgenic mice deficient in mTR (telomerase), XPD (important for nucleotide excision repair) or Ku80 (important for nonhomologous end-joining) (Rossi et al., 2005; Rossi et al., 2007).”
BackgroundInfluentialRejuvenation of aged hematopoietic stem cells
Guidi, N., & Geiger, H. (2016) · Seminars in Hematology · doi:10.1053/j.seminhematol.2016.10.005 · Cited by 29
“Epigenetic mechanism are thus also involved in HSCs aging in which several genes for myeloid cell differentiation become upregulated on the expense of lymphopoiesis genes, which are downregulated [10].”
Vitamin K antagonism impairs the bone marrow microenvironment and hematopoiesis
Verma, D., Kumar, R., Pereira, R. S., Karantanou, C., Zanetti, C., Minciacchi, V. R., Fulzele, K. S., Kunz, K., Hoelper, S., Chahabi, S. Z., et al. (2019) · Blood · doi:10.1182/blood.2018874214 · Cited by 29
Considering Cause and Effect of Immune Cell Aging on Cardiac Repair after Myocardial Infarction
Tobin, S. W., Alibhai, F. J., Weisel, R. D., & Li, R. (2020) · Cells · doi:10.3390/cells9081894 · Cited by 30
“Aging progressively reduces the CLP population, CLP proliferation and B cell development [91,102].”
BackgroundInfluentialWu, T., Plett, P. A., Chua, H. L., Jacobsen, M. H., Sandusky, G. E., MacVittie, T. J., & Orschell, C. M. (2020) · Health Physics · doi:10.1097/hp.0000000000001352 · Cited by 31
“2019) and others (Rossi et al. 2005) have reported, despite declining functional potential (Morrison et al.”
BackgroundResultExercise to Mend Aged-tissue Crosstalk in Bone Targeting Osteoporosis & Osteoarthritis
Little, S. E., Rubin, J. E., Diekman, B. O., Rubin, C. T., McGrath, C., Pagnotti, G. M., Klett, E. L., & Styner, M. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.08.011 · Cited by 30
Kent, D. G., Dykstra, B. J., & Eaves, C. J. (2007) · Current Protocols in Stem Cell Biology · doi:10.1002/9780470151808.sc02a04s3 · Cited by 29
Sullivan, C., Chen, Y., Shan, Y., Hu, Y., Peng, C., Zhang, H., Kong, L., & Li, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026246 · Cited by 29
“To achieve this, HSCs must be regulated and maintained through assorted growth factors, cell cycle regulation, transcription factors, epigenetic modulation, and interactions with the microenvironment [1,2].”
BackgroundResultInfluential
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
