Extracellular Vesicles and Hematopoietic Stem Cell Aging

2021 ◽  
Author(s):  
Laura R. Goldberg
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Natural Aging ◽  
Cell Aging ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Effects Of Aging

Extracellular vesicles (EVs), important mediators of intercellular communication, play a critical role in modulating hematopoiesis within the bone marrow microenvironment. Although few studies have explicitly examined the connections between EVs and hematopoietic stem cell (HSC) aging, there is a growing body of evidence that implicates EVs in numerous age-related biologic processes and diseases. This, coupled with their tremendous capacity to influence hematopoiesis, suggests EVs may be key mediators of HSC aging. This review provides an overview of the effects of aging on HSCs, the role of EVs in aging in general, and then details key work in EV modulation of normal and malignant hematopoiesis, with a particular focus on how these effects may translate into the ability of EVs to drive HSC aging. Finally, it describes an exciting emerging literature that provides direct evidence for EV modulation of HSC phenotypes during natural aging and highlights their potential in HSC rejuvenation. Taken collectively, this body of research has profound implications for the future of HSC aging studies. More clearly defining how EVs modify HSC function in an age-dependent fashion and determining the molecular mechanisms by which they drive these age-related HSC phenotype changes will undoubtedly yield innovative strategies to delay or even reverse age-related hematologic dysfunction.

scholarly journals Role of HLA in Hematopoietic Stem Cell Transplantation

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Meerim Park ◽  
Jong Jin Seo
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Critical Role ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Hematopoietic Stem

The selection of hematopoietic stem cell transplantation (HSCT) donors includes a rigorous assessment of the availability and human leukocyte antigen (HLA) match status of donors. HLA plays a critical role in HSCT, but its involvement in HSCT is constantly in flux because of changing technologies and variations in clinical transplantation results. The increased availability of HSCT through the use of HLA-mismatched related and unrelated donors is feasible with a more complete understanding of permissible HLA mismatches and the role of killer-cell immunoglobulin-like receptor (KIR) genes in HSCT. The influence of nongenetic factors on the tolerability of HLA mismatching has recently become evident, demonstrating a need for the integration of both genetic and nongenetic variables in donor selection.

scholarly journals Engraftment of rare, pathogenic donor hematopoietic mutations in unrelated hematopoietic stem cell transplantation

2020 ◽  
Vol 12 (526) ◽  
pp. eaax6249 ◽  
Author(s):  
Wing Hing Wong ◽  
Sima Bhatt ◽  
Kathryn Trinkaus ◽  
Iskra Pusic ◽  
Kevin Elliott ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
High Throughput Sequencing ◽  
Limit Of Detection ◽  
Cell Transplant ◽  
Younger Adults ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Age Related ◽  
Over Time

Clonal hematopoiesis is associated with various age-related morbidities. Error-corrected sequencing (ECS) of human blood samples, with a limit of detection of ≥0.0001, has demonstrated that nearly every healthy individual >50 years old harbors rare hematopoietic clones below the detection limit of standard high-throughput sequencing. If these rare mutations confer survival or proliferation advantages, then the clone(s) could expand after a selective pressure such as chemotherapy, radiotherapy, or chronic immunosuppression. Given these observations and the lack of quantitative data regarding clonal hematopoiesis in adolescents and young adults, who are more likely to serve as unrelated hematopoietic stem cell donors, we completed this pilot study to determine whether younger adults harbored hematopoietic clones with pathogenic mutations, how often those clones were transferred to recipients, and what happened to these clones over time after transplantation. We performed ECS on 125 blood and marrow samples from 25 matched unrelated donors and recipients. Clonal mutations, with a median variant allele frequency of 0.00247, were found in 11 donors (44%; median, 36 years old). Of the mutated clones, 84.2% of mutations were predicted to be molecularly pathogenic and 100% engrafted in recipients. Recipients also demonstrated de novo clonal expansion within the first 100 days after hematopoietic stem cell transplant (HSCT). Given this pilot demonstration that rare, pathogenic clonal mutations are far more prevalent in younger adults than previously appreciated, and they engraft in recipients and persist over time, larger studies with longer follow-up are necessary to correlate clonal engraftment with post-HSCT morbidity.

scholarly journals Serial transplantation reveals a critical role for endoglin in hematopoietic stem cell quiescence

Blood ◽  
2019 ◽  
Vol 133 (7) ◽  
pp. 688-696 ◽  
Author(s):  
Luciene Borges ◽  
Vanessa K. P. Oliveira ◽  
June Baik ◽  
Sean C. Bendall ◽  
Rita C. R. Perlingeiro
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Hematopoietic Stem ◽  
Conditional Deletion ◽  
Stem Cell Quiescence ◽  
Β Receptor ◽  
Serial Transplantation

Abstract Transforming growth factor β (TGF-β) is well known for its important function in hematopoietic stem cell (HSC) quiescence. However, the molecular mechanism underlining this function remains obscure. Endoglin (Eng), a type III receptor for the TGF-β superfamily, has been shown to selectively mark long-term HSCs; however, its necessity in adult HSCs is unknown due to embryonic lethality. Using conditional deletion of Eng combined with serial transplantation, we show that this TGF-β receptor is critical to maintain the HSC pool. Transplantation of Eng-deleted whole bone marrow or purified HSCs into lethally irradiated mice results in a profound engraftment defect in tertiary and quaternary recipients. Cell cycle analysis of primary grafts revealed decreased frequency of HSCs in G0, suggesting that lack of Eng impairs reentry of HSCs to quiescence. Using cytometry by time of flight (CyTOF) to evaluate the activity of signaling pathways in individual HSCs, we find that Eng is required within the Lin−Sca+Kit+–CD48− CD150+ fraction for canonical and noncanonical TGF-β signaling, as indicated by decreased phosphorylation of SMAD2/3 and the p38 MAPK-activated protein kinase 2, respectively. These findings support an essential role for Eng in positively modulating TGF-β signaling to ensure maintenance of HSC quiescence.

scholarly journals Human and Murine Hematopoietic Stem Cell Aging Is Associated with Functional Impairments and Intrinsic Megakaryocytic/Erythroid Bias

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0158369 ◽  
Author(s):  
Alexandra Rundberg Nilsson ◽  
Shamit Soneji ◽  
Sofia Adolfsson ◽  
David Bryder ◽  
Cornelis Jan Pronk
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Aging ◽  
Functional Impairments ◽  
Hematopoietic Stem ◽  
Stem Cell Aging ◽  
Murine Hematopoietic Stem Cell

Noncoding RNA and Epigenetic Change in Hematopoietic Stem Cell Aging

2017 ◽  
pp. 1-29
Author(s):  
David Garrick ◽  
Antoine David ◽  
Christelle Freitas ◽  
Dounia Djeghloul ◽  
Michele Goodhardt
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Noncoding Rna ◽  
Cell Aging ◽  
Epigenetic Change ◽  
Hematopoietic Stem ◽  
Stem Cell Aging

scholarly journals Causes and Mechanisms of Hematopoietic Stem Cell Aging

2019 ◽  
Vol 20 (6) ◽  
pp. 1272 ◽  
Author(s):  
Jungwoon Lee ◽  
Suk Yoon ◽  
Inpyo Choi ◽  
Haiyoung Jung
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
The Elderly ◽  
Cell Aging ◽  
Extrinsic Factors ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Stem Cell Aging ◽  
Related Stress

Many elderly people suffer from hematological diseases known to be highly age-dependent. Hematopoietic stem cells (HSCs) maintain the immune system by producing all blood cells throughout the lifetime of an organism. Recent reports have suggested that HSCs are susceptible to age-related stress and gradually lose their self-renewal and regeneration capacity with aging. HSC aging is driven by cell-intrinsic and -extrinsic factors that result in the disruption of the immune system. Thus, the study of HSC aging is important to our understanding of age-related immune diseases and can also provide potential strategies to improve quality of life in the elderly. In this review, we delineate our understanding of the phenotypes, causes, and molecular mechanisms involved in HSC aging.

Hematopoietic stem cell aging

2014 ◽  
Vol 29 ◽  
pp. 86-92 ◽  
Author(s):  
Hartmut Geiger ◽  
Michael Denkinger ◽  
Reinhold Schirmbeck
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Aging ◽  
Hematopoietic Stem ◽  
Stem Cell Aging
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