The DOI matches its Crossref record; 101 of the 108 references it cites were found in a registry or an index, and 7 are not checked yet; 4 of the 101 sources its claims cite were checked for support.
Aging of hematopoietic stem cells
Open accessAbstract
Hematopoietic stem cells (HSCs) ensure a balanced production of all blood cells throughout life. As they age, HSCs gradually lose their self-renewal and regenerative potential, whereas the occurrence of cellular derailment strongly increases. Here we review our current understanding of the molecular mechanisms that contribute to HSC aging. We argue that most of the causes that underlie HSC aging result from cell-intrinsic pathways, and reflect on which aspects of the aging process may be reversible. Because many hematological pathologies are strongly age-associated, strategies to intervene in aspects of the stem cell aging process may have significant clinical relevance.
Verified 2026-10-06 · 7 references not checked yet
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Claims the paper makes
50 Not checked yet · 23 Own interpretation · 2 Partly supported · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Epigenetic genes that are relatively frequently affected in these conditions include DNMT3A, EZH2, TET2, and SETDB1.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Epigenetic reprogramming
What the sources say
- Partly supportedcites [74] Zink, 2017, Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly, Blood sourceExperimental — accuracy not yet measured
The ‘Association of driver mutations with clonal hematopoiesis’ section reports frequent mutations in DNMT3A and TET2 (93 and 76 individuals, respectively). Figure 2 includes SETDB1 among genes with detected mutations, but does not establish that it was relatively frequent; the passages do not report EZH2 as a frequently affected gene. Thus the paper supports only part of the four-gene list. (LLM, conf=0.88)
- Partly supportedcites [75] Xie, 2014, Age-related mutations associated with clonal hematopoietic expansion and malignancies, Nat Med sourceExperimental — accuracy not yet measured
The Results section on mutation frequencies reports that DNMT3A and TET2 were consistently mutated across the studied cohorts. It does not identify EZH2 or SETDB1 as relatively frequently affected; searches for both names found no supporting passage in our copy. Page numbers were not provided. (LLM, conf=0.88)
- Partly supportedcites [76] Jaiswal, 2014, Age-related clonal hematopoiesis associated with adverse outcomes, N Engl J Med sourceExperimental — accuracy not yet measured
The Results section (page unavailable) identifies DNMT3A and TET2 among the most commonly mutated genes, supporting those two examples. It names ASXL1 next, not EZH2 or SETDB1; searches for EZH2 and SETDB1 found no passage establishing either as relatively frequently affected. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
None of the sources cited for this claim have been checked yet.
In the paper
“young bone marrow cells, when transplanted into aged recipients, engraft worse than when transplanted into young recipients.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Cell-intrinsic vs cell-extrinsic mechanisms
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“the functional heterogeneity of the HSC population increases with age.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Heterogeneity of HSC aging
What the sources say
- Not checked yetcites [10] Dykstra, 2011, Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells, J Exp Med source
- Not checked yetcites [13] Sudo, 2000, Age-associated characteristics of murine hematopoietic stem cells, J Exp Med source
- Not checked yetcites [17] Beerman, 2010, Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion, Proc Natl Acad Sci USA source
- Not checked yetcites [32] Cho, 2008, A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells, Blood source
- Not checked yetcites [33] Ho, 2017, Autophagy maintains the metabolism and function of young and old stem cells, Nature source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“aging (also of the hematopoietic system) is at least qualitatively different in distinct strains of mice.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
What the sources say
- Not checked yetcites [30] De Haan, 1999, Genetic analysis of hemopoietic cell cycling in mice suggests its involvement in organismal life span, FASEB J source
- Not checked yetcites [31] de Haan, 1997, Intrinsic and extrinsic control of hemopoietic stem cell numbers: mapping of a stem cell gene, J Exp Med source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“hematological malignancies can result from a defective bone marrow environment.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Cell-intrinsic vs cell-extrinsic mechanisms
What the sources say
- Not checked yetcites [44] Zambetti, 2016, Mesenchymal inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia, Cell Stem Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“most of the proliferative burden resides with committed progenitors”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“transplanting aged HSCs in a young environment apparently cannot reverse these changes.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Cell-intrinsic vs cell-extrinsic mechanisms
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“in aged mice that display an overall increase in HSC pool size”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Heterogeneity of HSC aging
What the sources say
- Not checked yetcites [10] Dykstra, 2011, Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells, J Exp Med source
- Not checked yetcites [13] Sudo, 2000, Age-associated characteristics of murine hematopoietic stem cells, J Exp Med source
- Not checked yetcites [17] Beerman, 2010, Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion, Proc Natl Acad Sci USA source
- Not checked yetcites [32] Cho, 2008, A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells, Blood source
- Not checked yetcites [33] Ho, 2017, Autophagy maintains the metabolism and function of young and old stem cells, Nature source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“aged HSC accumulate signatures of widespread DNA damage, including g-H2AX foci.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > DNA damage
What the sources say
- Not checked yetcites [49] Walter, 2015, Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells, Nature source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“in healthy elderly individuals, DNA mutations in specific loci are associated with the establishment of clonal hematopoiesis”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > DNA damage
What the sources say
- Not checked yetcites [52] Steensma, 2015, Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes, Blood source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 14
- Probably not a substantial claim. 4
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The genetic or pharmacological depletion of senescent cells in mice has been shown to enhance regenerative potential and extend life span.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Senescence
What the sources say
- Partly supportedcites [57] Baker, 2016, Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan, Nature sourceExperimental — accuracy not yet measured
The Discussion reports that clearing p16Ink4a-positive cells with the INK-ATTAC system extended median lifespan in mice. The fat-progenitor results show preservation of adipogenesis-related measures, but not a general increase in regenerative potential; Extended Data Figure 10 reports that clearance during wound healing delayed wound closure. The study used a drug to activate a genetic clearance system, rather than demonstrating a separate pharmacological depletion method. (LLM, conf=0.88)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the pool of stem cells with reduced potential increases to compensate for loss of function of individual stem cells”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“the involvement of telomere shortening in the functional decline of HSC is particularly evident in human”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > DNA damage
What the sources say
- Not checked yetcites [53] Aubert, 2008, Telomeres and aging, Physiol Rev source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although some of these cell-intrinsic causes of aging are unlikely to be reversible, several others might allow interventions and thus could potentially be explored for pharmacological targeting”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Cell-intrinsic mechanisms that cause HSC aging
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“an age-dependent increase in the frequency of putative stem cells, coinciding with impaired functionality and reduced lymphoid potential, has also been in the human system.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
What the sources say
- Not checked yetcites [27] Kuranda, 2011, Age-related changes in human hematopoietic stem/progenitor cells, Aging Cell source
- Not checked yetcites [28] Pang, 2011, Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age, Proc Natl Acad Sci USA source
- Not checked yetcites [29] Rundberg Nilsson, 2016, Human and murine hematopoietic stem cell aging is associated with functional impairments and intrinsic megakaryocytic/erythroid bias, PLoS One source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“telomeres progressively shorten in human HSCs isolated from fetal liver, cord blood, or adult bone marrow, which is associated with a strongly reduced proliferative potential.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
What the sources say
- Not checked yetcites [26] Vaziri, 1994, Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age, Proc Natl Acad Sci USA source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“with each cell division, the potential of a HSC to contribute to blood cell production declines”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“during steady-state hematopoiesis the most primitive stem cells are largely inactive.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
What the sources say
- Not checked yetcites [18] Van Zant, 1984, Studies of hematopoietic stem cells spared by 5-fluorouracil, J Exp Med source
- Not checked yetcites [19] Bradford, 1997, Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment, Exp Hematol
- Not checked yetcites [20] Cheshier, 1999, In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells, Proc Natl Acad Sci USA source
- Not checked yetcites [21] Dykstra, 2007, Long-term propagation of distinct hematopoietic differentiation programs in vivo, Cell Stem Cell source
- Not checked yetcites [22] Morita, 2010, Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment, J Exp Med source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“in effect they are likely to be highly interdependent and interconnected.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Cell-intrinsic mechanisms that cause HSC aging
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The most irreversible cause of HSC aging relates to the accumulation of random DNA damage.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > DNA damage
plaindirect- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“clonal hematopoiesis in otherwise healthy individuals increases the risk to develop leukemia, and, interestingly, cardiovascular disease, and thus is associated with increased mortality.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
What the sources say
- Not checked yetcites [74] Zink, 2017, Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly, Blood source
- Not checked yetcites [75] Xie, 2014, Age-related mutations associated with clonal hematopoietic expansion and malignancies, Nat Med source
- Not checked yetcites [76] Jaiswal, 2014, Age-related clonal hematopoiesis associated with adverse outcomes, N Engl J Med source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“clonal hematopoiesis has been associated with increased incidence of atherosclerotic cardiovascular disease, suggesting that the function of monocytic cells derived from these aged stem cell clones is impaired.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“high levels of reactive oxygen species, generated by mitochondria, accumulate in aged HSCs and compromise their functioning.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Impaired autophagy and mitochondrial activity
What the sources say
- Not checked yetcites [61] Ito, 2006, Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells, Nat Med source
- Not checked yetcites [62] Mohrin, 2015, Stem cell aging. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging, Science source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“aged red cells and aged platelets display impaired functioning”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
What the sources say
- Not checked yetcites [82] Hoehn, 2015, Molecular mechanisms of erythrocyte aging, Biol Chem source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“impaired autophagy in aged HSCs appears to specifically result in the accumulation of mitochondria, which in turn induces metabolic stress.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Impaired autophagy and mitochondrial activity
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“pharmacological interventions in these signaling pathways are feasible and may be exploited to restore function in aged HSCs.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Impaired autophagy and mitochondrial activity
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“mutations in genes encoding for epigenetic enzymes have been found in either elderly people whose hematopoietic system has become oligoclonal, or in patients with myelodysplastic syndromes or acute myeloid leukemia.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Epigenetic reprogramming
What the sources say
- Not checked yetcites [52] Steensma, 2015, Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes, Blood source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mitochondrial dysfunctioning caused by accumulating mitochondrial DNA mutations has been shown to cause multiple hematopoietic defects that are typically seen in the elderly, but HSCs themselves appear to relatively resistant.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Impaired autophagy and mitochondrial activity
What the sources say
- Not checked yetcites [63] Norddahl, 2011, Accumulating mitochondrial DNA mutations drive premature hematopoietic aging phenotypes distinct from physiological stem cell aging, Cell Stem Cell source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The formation of blood cells in mice and humans is conceptually identical.
“decades of research have shown that, conceptually, the formation of blood cells in mouse and human is identical”
The paper relies on this without support.
Many hematological conditions are strongly age-dependent.
“many hematological conditions are strongly age-dependent.”
The paper relies on this without support.
The purity of HSCs in transplantation experiments is never more than 50%.
“the purity of HSCs, at least when assayed in transplantation experiments, is never more than 50%.”
The paper relies on this without support.
Even after the most stringent enrichment protocols, many non-HSCs remain.
“even after the most stringent enrichment protocols, many non-HSCs (mostly progenitors) remain.”
The paper relies on this without support.
Genetic disparities are likely to be prominent in humans.
“These genetic disparities are also likely to be prominent in human.”
The paper relies on this without support.
During steady-state in vivo hematopoiesis, no conversion of hematopoietic progenitors into stem cells has been reported.
“but in the hematopoietic system such progenitor-to-stem cell conversions have never been described, at least not during steadystate in vivo hematopoiesis.”
The authors state this as an assumption.
Human HSC aging is not fundamentally different from mouse HSC aging.
“Assuming that in human HSC aging is not fundamentally different than in mice”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, aged HSCs have been shown to have lower regenerative potential and skewed differentiation toward the myeloid lineage instead of the lymphoid lineage [88].”
From Osteoimmunology of Fracture Healing. (2024) · cites this paper as [88]
Citations
Cites
1 retracted
Systemic signals regulate ageing and rejuvenation of blood stem cell niches
Mayack, S. R., Shadrach, J. L., Kim, F. S., & Wagers, A. J. (2010) · Nature · doi:10.1038/nature08749 · Cited by 137
RetractedLópez-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982
Age-related clonal hematopoiesis associated with adverse outcomes
Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., Lindsley, R. C., Mermel, C. H., Burtt, N., Chavez, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408617 · Cited by 4,841
Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence
Genovese, G., Kähler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., Chambert, K., Mick, E., Neale, B. M., Fromer, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409405 · Cited by 3,531
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,876
Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease
Jaiswal, S., Natarajan, P., Silver, A. J., Gibson, C. J., Bick, A. G., Shvartz, E., McConkey, M., Gupta, N., Gabriel, S., Ardissino, D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1701719 · Cited by 2,683
Cellular senescence in aging and age-related disease: from mechanisms to therapy
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015) · Nature Medicine · doi:10.1038/nm.4000 · Cited by 2,363
Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes
Steensma, D. P., Bejar, R., Jaiswal, S., Lindsley, R. C., Sekeres, M. A., Hasserjian, R. P., & Ebert, B. L. (2015) · Blood · doi:10.1182/blood-2015-03-631747 · Cited by 1,971
Age-related mutations associated with clonal hematopoietic expansion and malignancies
Xie, M., Lu, C., Wang, J., McLellan, M. D., Johnson, K. J., Wendl, M. C., McMichael, J. F., Schmidt, H. K., Yellapantula, V., Miller, C. A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3733 · Cited by 1,874
Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4010 · Cited by 1,819
Lgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro
Barker, N., Huch, M., Kujala, P., van de Wetering, M., Snippert, H. J., van Es, J. H., Sato, T., Stange, D. E., Begthel, H., van den Born, M., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2009.11.013 · Cited by 1,547
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice
Fuster, J. J., MacLauchlan, S., Zuriaga, M. A., Polackal, M. N., Ostriker, A. C., Chakraborty, R., Wu, C.-L., Sano, S., Muralidharan, S., Rius, C., et al. (2017) · Science · doi:10.1126/science.aag1381 · Cited by 1,536
Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells
Ito, K., Hirao, A., Arai, F., Takubo, K., Matsuoka, S., Miyamoto, K., Ohmura, M., Naka, K., Hosokawa, K., Ikeda, Y., et al. (2006) · Nature Medicine · doi:10.1038/nm1388 · Cited by 1,362
Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice
Rudolph, K. L., Chang, S., Lee, H.-W., Blasco, M., Gottlieb, G. J., Greider, C., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80580-2 · Cited by 1,349
The intestinal crypt, a prototype stem cell compartment
Clevers, H. (2013) · Cell · doi:10.1016/j.cell.2013.07.004 · Cited by 1,223
Aubert, G., & Lansdorp, P. M. (2008) · Physiological Reviews · doi:10.1152/physrev.00026.2007 · Cited by 1,188
Cell 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
Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age.
Vaziri, H., Dragowska, W., Allsopp, R. C., Thomas, T. E., Harley, C. B., & Lansdorp, P. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.21.9857 · Cited by 1,132
Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age
Rossi, D. J., Bryder, D., Seita, J., Nussenzweig, A., Hoeijmakers, J., & Weissman, I. L. (2007) · Nature · doi:10.1038/nature05862 · Cited by 1,115
Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice
Villeda, S. A., Plambeck, K. E., Middeldorp, J., Castellano, J. M., Mosher, K. I., Luo, J., Smith, L. K., Bieri, G., Lin, K., Berdnik, D., et al. (2014) · Nature Medicine · doi:10.1038/nm.3569 · Cited by 1,081
Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors
Katsimpardi, L., Litterman, N. K., Schein, P. A., Miller, C. M., Loffredo, F. S., Wojtkiewicz, G. R., Chen, J. W., Lee, R. T., Wagers, A. J., & Rubin, L. L. (2014) · Science · doi:10.1126/science.1251141 · Cited by 1,037
Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age
Pang, W. W., Price, E. A., Sahoo, D., Beerman, I., Maloney, W. J., Rossi, D. J., Schrier, S. L., & Weissman, I. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116110108 · Cited by 991
Tissue-specific mutation accumulation in human adult stem cells during life
Blokzijl, F., de Ligt, J., Jager, M., Sasselli, V., Roerink, S., Sasaki, N., Huch, M., Boymans, S., Kuijk, E., Prins, P., et al. (2016) · Nature · doi:10.1038/nature19768 · Cited by 935
Autophagy maintains the metabolism and function of young and old stem cells
Ho, T. T., Warr, M. R., Adelman, E. R., Lansinger, O. M., Flach, J., Verovskaya, E. V., Figueroa, M. E., & Passegué, E. (2017) · Nature · doi:10.1038/nature21388 · Cited by 896
In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells
Cheshier, S. H., Morrison, S. J., Liao, X., & Weissman, I. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3120 · Cited by 858
The aging of hematopoietic stem cells
Morrison, S. J., Wandycz, A. M., Akashi, K., Globerson, A., & Weissman, I. L. (1996) · Nature Medicine · doi:10.1038/nm0996-1011 · Cited by 853
Aging 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 806
Clonal dynamics of native haematopoiesis
Sun, J., Ramos, A., Chapman, B., Johnnidis, J. B., Le, L., Ho, Y.-J., Klein, A. M., Hofmann, O., & Camargo, F. D. (2014) · Nature · doi:10.1038/nature13824 · Cited by 803
Kowalczyk, M. S., Tirosh, I., Heckl, D., Rao, T. N., Dixit, A., Haas, B. J., Schneider, R. K., Wagers, A. J., Ebert, B. L., & Regev, A. (2015) · Genome Research · doi:10.1101/gr.192237.115 · Cited by 778
Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly
Zink, F., Stacey, S. N., Norddahl, G. L., Frigge, M. L., Magnusson, O. T., Jonsdottir, I., Thorgeirsson, T. E., Sigurdsson, A., Gudjonsson, S. A., Gudmundsson, J., et al. (2017) · Blood · doi:10.1182/blood-2017-02-769869 · Cited by 777
Fundamental properties of unperturbed haematopoiesis from stem cells in vivo
Busch, K., Klapproth, K., Barile, M., Flossdorf, M., Holland-Letz, T., Schlenner, S. M., Reth, M., Höfer, T., & Rodewald, H.-R. (2015) · Nature · doi:10.1038/nature14242 · Cited by 769
Yamamoto, R., Morita, Y., Ooehara, J., Hamanaka, S., Onodera, M., Rudolph, K. L., Ema, H., & Nakauchi, H. (2013) · Cell · doi:10.1016/j.cell.2013.08.007 · Cited by 745
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
Beerman, 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
Sun, D., Luo, M., Jeong, M., Rodriguez, B., Xia, Z., Hannah, R., Wang, H., Le, T., Faull, K. F., Chen, R., et al. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.03.002 · Cited by 686
Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells
Flach, J., Bakker, S. T., Mohrin, M., Conroy, P. C., Pietras, E. M., Reynaud, D., Alvarez, S., Diolaiti, M. E., Ugarte, F., Forsberg, E. C., et al. (2014) · Nature · doi:10.1038/nature13619 · Cited by 650
Long-Term Propagation of Distinct Hematopoietic Differentiation Programs In Vivo
Dykstra, B. J., Kent, D. G., Bowie, M. B., McCaffrey, L., Hamilton, M. J., Lyons, K., Lee, S.-J., Brinkman, R. R., & Eaves, C. J. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.05.015 · Cited by 632
Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells
Walter, D., Lier, A., Geiselhart, A., Thalheimer, F. B., Huntscha, S., Sobotta, M. C., Moehrle, B., Brocks, D., Bayindir, I., Kaschutnig, P., et al. (2015) · Nature · doi:10.1038/nature14131 · Cited by 619
The ageing haematopoietic stem cell compartment
Geiger, H., de Haan, G., & Florian, M. C. (2013) · Nature Reviews Immunology · doi:10.1038/nri3433 · Cited by 604
Tetteh, P. W., Basak, O., Farin, H. F., Wiebrands, K., Kretzschmar, K., Begthel, H., van den Born, M., Korving, J., de Sauvage, F., van Es, J. H., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.01.001 · Cited by 575
Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation
Florian, M. C., Dörr, K., Niebel, A., Daria, D., Schrezenmeier, H., Rojewski, M., Filippi, M.-D., Hasenberg, A., Gunzer, M., Scharffetter-Kochanek, K., et al. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.04.007 · Cited by 564
Nonrandom X-inactivation patterns in normal females: lyonization ratios vary with age
Busque, L., Mio, R., Mattioli, J., Brais, E., Blais, N., Lalonde, Y., Maragh, M., & Gilliland, D. (1996) · Blood · doi:10.1182/blood.v88.1.59.59 · Cited by 543
Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1
Iwama, A., Oguro, H., Negishi, M., Kato, Y., Morita, Y., Tsukui, H., Ema, H., Kamijo, T., Katoh-Fukui, Y., Koseki, H., et al. (2004) · Immunity · doi:10.1016/j.immuni.2004.11.004 · Cited by 515
Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells
Dykstra, B., Olthof, S., Schreuder, J., Ritsema, M., & de Haan, G. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20111490 · Cited by 494
A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging
Mohrin, M., Shin, J., Liu, Y., Brown, K., Luo, H., Xi, Y., Haynes, C. M., & Chen, D. (2015) · Science · doi:10.1126/science.aaa2361 · Cited by 490
Beerman, I., Bock, C., Garrison, B. S., Smith, Z. D., Gu, H., Meissner, A., & Rossi, D. J. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.01.017 · Cited by 485
Wilson, N. K., Kent, D. G., Buettner, F., Shehata, M., Macaulay, I. C., Calero-Nieto, F. J., Sánchez Castillo, M., Oedekoven, C. A., Diamanti, E., Schulte, R., et al. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.04.004 · Cited by 466
Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment
Morita, Y., Ema, H., & Nakauchi, H. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20091318 · Cited by 456
Lu, R., Neff, N. F., Quake, S. R., & Weissman, I. L. (2011) · Nature Biotechnology · doi:10.1038/nbt.1977 · Cited by 451
Human umbilical cord plasma proteins revitalize hippocampal function in aged mice
Castellano, J. M., Mosher, K. I., Abbey, R. J., McBride, A. A., James, M. L., Berdnik, D., Shen, J. C., Zou, B., Xie, X. S., Tingle, M., et al. (2017) · Nature · doi:10.1038/nature22067 · Cited by 445
Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment.
Bradford, G. B., Williams, B., Rossi, R., & Bertoncello, I. (1997) · PubMed · Cited by 419
Diverse and heritable lineage imprinting of early haematopoietic progenitors
Naik, S. H., Perié, L., Swart, E., Gerlach, C., van Rooij, N., de Boer, R. J., & Schumacher, T. N. (2013) · Nature · doi:10.1038/nature12013 · Cited by 416
Cho, R. H., Sieburg, H. B., & Muller-Sieburg, C. E. (2008) · Blood · doi:10.1182/blood-2007-11-123547 · Cited by 377
The polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion
Kamminga, L. M., Bystrykh, L. V., de Boer, A., Houwer, S., Douma, J., Weersing, E., Dontje, B., & de Haan, G. (2006) · Blood · doi:10.1182/blood-2005-09-3585 · Cited by 376
Inflamm-aging of hematopoiesis, hematopoietic stem cells, and the bone marrow microenvironment
Kovtonyuk, L. V., Fritsch, K., Feng, X., Manz, M. G., & Takizawa, H. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00502 · Cited by 371
Grover, A., Sanjuán-Pla, A., Thongjuea, S., Carrelha, J., Giustacchini, A., Gambardella, A. R., Macaulay, I. C., Mancini, E., Luis, T. C., Mead, A. J., et al. (2016) · Nature Communications · doi:10.1038/ncomms11075 · Cited by 361
Goodell, M. A., & Rando, T. A. (2015) · Science · doi:10.1126/science.aab3388 · Cited by 347
Zambetti, N. A., Ping, Z., Chen, S., Kenswil, K. J. G., Mylona, M. A., Sanders, M. A., Hoogenboezem, R. M., Bindels, E. M. J., Adisty, M. N., Van Strien, P. M. H., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.08.021 · Cited by 342
Reprogramming Committed Murine Blood Cells to Induced Hematopoietic Stem Cells with Defined Factors
Riddell, J., Gazit, R., Garrison, B. S., Guo, G., Saadatpour, A., Mandal, P. K., Ebina, W., Volchkov, P., Yuan, G.-C., Orkin, S. H., et al. (2014) · Cell · doi:10.1016/j.cell.2014.04.006 · Cited by 323
Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammation
Takizawa, H., Regoes, R. R., Boddupalli, C. S., Bonhoeffer, S., & Manz, M. G. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20101643 · Cited by 309
Hematopoietic stem cells count and remember self-renewal divisions
Bernitz, J. M., Kim, H. S., MacArthur, B., Sieburg, H., & Moore, K. (2016) · Cell · doi:10.1016/j.cell.2016.10.022 · Cited by 285
Ju, Z., Jiang, H., Jaworski, M., Rathinam, C., Gompf, A., Klein, C., Trumpp, A., & Rudolph, K. L. (2007) · Nature Medicine · doi:10.1038/nm1578 · Cited by 284
Harrison, D. E., & Astle, C. M. (1982) · The Journal of Experimental Medicine · doi:10.1084/jem.156.6.1767 · Cited by 281
Rantes/Ccl5 influences hematopoietic stem cell subtypes and causes myeloid skewing
Ergen, A. V., Boles, N. C., & Goodell, M. A. (2012) · Blood · doi:10.1182/blood-2011-11-391730 · Cited by 280
Conboy, M. J., Conboy, I. M., & Rando, T. A. (2013) · Aging Cell · doi:10.1111/acel.12065 · Cited by 265
Cellular barcoding tool for clonal analysis in the hematopoietic system
Gerrits, A., Dykstra, B. J., Kalmykowa, O. J., Klauke, K., Verovskaya, E. V., Broekhuis, M., de Haan, G., & Bystrykh, L. V. (2010) · Blood · doi:10.1182/blood-2009-06-229757 · Cited by 253
Norddahl, G. L., Pronk, C. J., Wahlestedt, M., Sten, G., Nygren, J. M., Ugale, A., Sigvardsson, M., & Bryder, D. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2011.03.009 · Cited by 249
Telomere length is associated with disease severity and declines with age in dyskeratosis congenita
Alter, B. P., Rosenberg, P. S., Giri, N., Baerlocher, G. M., Lansdorp, P. M., & Savage, S. A. (2012) · Haematologica · doi:10.3324/haematol.2011.055269 · Cited by 238
Klauke, K., Radulović, V., Broekhuis, M., Weersing, E., Zwart, E., Olthof, S., Ritsema, M., Bruggeman, S., Wu, X., Helin, K., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2701 · Cited by 237
Dnmt3a loss predisposes murine hematopoietic stem cells to malignant transformation
Mayle, A., Yang, L., Rodriguez, B., Zhou, T., Chang, E., Curry, C. V., Challen, G. A., Li, W., Wheeler, D., Rebel, V. I., et al. (2015) · Blood · doi:10.1182/blood-2014-08-594648 · Cited by 235
Functional antagonism of the polycomb-group genes eed and Bmi1 in hemopoietic cell proliferation
Lessard, J., Schumacher, A., Thorsteinsdottir, U., van Lohuizen, M., Magnuson, T., & Sauvageau, G. (1999) · Genes & Development · doi:10.1101/gad.13.20.2691 · Cited by 219
Induction of a hemogenic program in mouse fibroblasts
Pereira, C.-F., Chang, B., Qiu, J., Niu, X., Papatsenko, D., Hendry, C. E., Clark, N. R., Nomura-Kitabayashi, A., Kovacic, J. C., Ma’ayan, A., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.05.024 · Cited by 216
How I treat the older patient with acute myeloid leukemia
Ossenkoppele, G. J., & Löwenberg, B. (2014) · Blood · doi:10.1182/blood-2014-08-551499 · Cited by 215
Ema, H., Sudo, K., Seita, J., Matsubara, A., Morita, Y., Osawa, M., Takatsu, K., Τακακι, S., & Nakauchi, H. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.03.019 · Cited by 215
Studies of hematopoietic stem cells spared by 5-fluorouracil.
Zant, G. V. (1984) · The Journal of Experimental Medicine · doi:10.1084/jem.159.3.679 · Cited by 210
Epigenetic Memory Underlies Cell-Autonomous Heterogeneous Behavior of Hematopoietic Stem Cells
Yu, V. W. C., Yusuf, R. Z., Oki, T., Wu, J. W., Sáez, B., Wang, X., Cook, C., Baryawno, N., Ziller, M. J., Lee, E., et al. (2016) · Cell · doi:10.1016/j.cell.2016.10.045 · Cited by 207
Age-related changes in human hematopoietic stem/progenitor cells
Kuranda, K., Vargaftig, J., Rochère, P. D. L., Dosquet, C., Charron, D. J., Bardin, F., Tonnelle, C., Bonnet, D. A., & Goodhardt, M. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00675.x · Cited by 177
Verovskaya, E. V., Broekhuis, M., Zwart, E., Ritsema, M., van Os, R. P., de Haan, G., & Bystrykh, L. V. (2013) · Blood · doi:10.1182/blood-2013-01-481135 · Cited by 175
Champion, K. M., Gilbert, J. G. R., Asimakopoulos, F. A., Hinshelwood, S., & Green, A. R. (1997) · British Journal of Haematology · doi:10.1046/j.1365-2141.1997.1933010.x · Cited by 171
Nilsson, A. R., Soneji, S., Adolfsson, S., Bryder, D., & Pronk, C. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158369 · Cited by 161
Effect of TERT over-expression on the long-term transplantation capacity of hematopoietic stem cells
Allsopp, R. C., Morin, G. B., Horner, J. W., DePinho, R., Harley, C. B., & Weissman, I. L. (2003) · Nature Medicine · doi:10.1038/nm0403-369 · Cited by 155
Numbers and functions of transplantable primitive immunohematopoietic stem cells. Effects of age.
Harrison, D. E., Astle, C. M., & Stone, M. (1989) · The Journal of Immunology · doi:10.4049/jimmunol.142.11.3833 · Cited by 148
Proliferative capacity of murine hematopoietic stem cells.
Hellman, S., Botnick, L. E., Hannon, E. C., & Vigneulle, R. M. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.1.490 · Cited by 148
Opposing roles of polycomb repressive complexes in hematopoietic stem and progenitor cells
Majewski, I. J., Ritchie, M. E., Phipson, B., Corbin, J., Pakusch, M., Ebert, A., Busslinger, M., Koseki, H., Hu, Y., Smyth, G. K., et al. (2010) · Blood · doi:10.1182/blood-2009-12-260760 · Cited by 135
Intrinsic and extrinsic control of hemopoietic stem cell numbers: mapping of a stem cell gene
Haan, G. D., & Zant, G. V. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.4.529 · Cited by 134
Clonal fate mapping quantifies the number of haematopoietic stem cells that arise during development
Henninger, J. E., Santoso, B., Hans, S., Durand, E. M., Moore, J. L., Mosimann, C., Brand, M., Traver, D. J., & Zon, L. I. (2016) · Nature Cell Biology · doi:10.1038/ncb3444 · Cited by 116
Cheung, A. M. S., Nguyen, L. V., Carles, A., Beer, P. A., Miller, P. H., Knapp, D. J. H. F., Dhillon, K., Hirst, M., & Eaves, C. J. (2013) · Blood · doi:10.1182/blood-2013-06-508432 · Cited by 111
Wahlestedt, M., Norddahl, G. L., Sten, G., Ugale, A., Frisk, M.-A. M., Mattsson, R., Deierborg, T., Sigvardsson, M., & Bryder, D. (2013) · Blood · doi:10.1182/blood-2012-11-469080 · Cited by 106
Age- and stage-specific regulation patterns in the hematopoietic stem cell hierarchy
Geiger, H., True, J. M., de Haan, G., & Zant, G. E. V. (2001) · Blood · doi:10.1182/blood.v98.10.2966 · Cited by 103
Van Zant, G., Holland, B. P., Eldridge, P. W., & Chen, J. J. (1990) · The Journal of Experimental Medicine · doi:10.1084/jem.171.5.1547 · Cited by 99
Decline in bone marrow proliferative capacity as a function of age
Mauch, P., Botnick, L., Hannon, E. C., Obbagy, J., & Hellman, S. (1982) · Blood · doi:10.1182/blood.v60.1.245.245 · Cited by 92
de Haan, G., & van Zant, G. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.6.707 · Cited by 87
Roeder, I., Kamminga, L. M., Braesel, K., Dontje, B., de Haan, G., & Loeffler, M. (2004) · Blood · doi:10.1182/blood-2004-01-0282 · Cited by 83
Counting stem cells: methodological constraints
Bystrykh, L. V., Verovskaya, E. V., Zwart, E., Broekhuis, M., & de Haan, G. (2012) · Nature Methods · doi:10.1038/nmeth.2043 · Cited by 80
Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult leukemia
Signer, R. A. J., Montecino-Rodriguez, E., Witte, O. N., McLaughlin, J., & Dorshkind, K. (2007) · Blood · doi:10.1182/blood-2007-01-069401 · Cited by 77
Hematopoietic stem cell ageing is uncoupled from p16INK4A-mediated senescence
Attema, J. L., Pronk, C. J. H., Norddahl, G. L., Nygren, J. M., & Bryder, D. (2009) · Oncogene · doi:10.1038/onc.2009.94 · Cited by 72
Clonal stability of blood cell lineages indicated by X-chromosomal transcriptional polymorphism.
Prchal, J. T., Prchal, J., Beličková, M., Chen, S., Guan, Y., Gartland, G. L., & Cooper, M. D. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.2.561 · Cited by 62
Wojtowicz, E. E., Lechman, E. R., Hermans, K. G., Schoof, E. M., Wienholds, E., Isserlin, R., van Veelen, P. A., Broekhuis, M. J. C., Janssen, G. M. C., Trotman-Grant, A., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.06.008 · Cited by 60
Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate
Wahlestedt, M., Erlandsson, E., Kristiansen, T., Lu, R., Brakebusch, C., Weissman, I. L., Yuan, J., Martin-Gonzalez, J., & Bryder, D. (2017) · Nature Communications · doi:10.1038/ncomms14533 · Cited by 59
Uncompromised 10-year survival of oldest old carrying somatic mutations in DNMT3A and TET2
van den Akker, E. B., Pitts, S. J., Deelen, J., Moed, M. H., Potluri, S., van Rooij, J., Suchiman, H. E. D., Lakenberg, N., de Dijcker, W. J., Uitterlinden, A. G., et al. (2016) · Blood · doi:10.1182/blood-2015-12-685925 · Cited by 49
Alternatives to stem cell renewal from a developmental viewpoint.
Zant, G. V., de Haan, G., & Rich, I. N. (1997) · PubMed · Cited by 48
Molecular mechanisms of erythrocyte aging
Hoehn, R. S., Jernigan, P. L., Chang, A. L., Edwards, M. J., & Pritts, T. A. (2015) · Biological Chemistry · doi:10.1515/hsz-2014-0292 · Cited by 47
Noda, S., Ichikawa, H., & Miyoshi, H. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.03.153 · Cited by 43
Stiehm, E. R., Roberts, R. L., Hanley-Lopez, J., Wakim, M. E., Pallavicini, M. G., Cowan, M. J., Ettenger, R. B., & Feig, S. A. (1996) · New England Journal of Medicine · doi:10.1056/nejm199612123352405 · Cited by 18
Wolf, N. S., Priestley, G. V., & Averill, L. E. (1983) · PubMed · Cited by 14
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
Decline in bone marrow proliferative capacity as a function of age
Mauch, P., Botnick, L., Hannon, E., et al. (1982) · Blood · doi:10.1182/blood.v60.1.245.bloodjournal601245 · Cited by 7
Haemopoiesis by clonal succession?
Rosendaal, M., & Adam, J. (1984) · PubMed · Cited by 7
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Facing up to the global challenges of ageing
Partridge, L., Deelen, J., & Slagboom, P. E. (2018) · Nature · doi:10.1038/s41586-018-0457-8 · Cited by 1,475
Haematopoietic stem cell activity and interactions with the niche
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TGF-β Signaling in Cellular Senescence and Aging-Related Pathology
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Metadata
- Authors
- de Haan, G., & Lazare, S. S.
- Affiliations
- European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- University Medical Center Groningen (NL)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2018-02-01
- Volume
- 131
- Issue
- 5
- Pages
- 479-487
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2768409010
- Semantic Scholar
- 767a7a803b0d377cfb03d909da859be3e4df29bc
- Cited by
- 432
- References
- 107
- Citations by year
- 2026: 41 · 2025: 46 · 2024: 68 · 2023: 62 · 2022: 55 · 2021: 67 · 2020: 51 · 2019: 27 · 2018: 15
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- European Commission (316964)
- ZonMw
- KWF Kankerbestrijding (2014-7178, RUG 2014-7178)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Keywords
- hematopoietic stem cells, stem cell aging, cellular senescence, self-renewal, regenerative capacity, molecular mechanisms of aging
- MeSH terms
- Aging, Animals, Autophagy, Hematopoiesis, Hematopoietic Stem Cells, Humans, Mitochondria, Cellular Senescence, Epigenesis, Genetic
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.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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 ›
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