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Published in: Journal of Hematology & Oncology 1/2020

Open Access 01-12-2020 | Epigenetics | Review

Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches

Authors: Lei Zhang, Ryan Mack, Peter Breslin, Jiwang Zhang

Published in: Journal of Hematology & Oncology | Issue 1/2020

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Abstract

Aging drives the genetic and epigenetic changes that result in a decline in hematopoietic stem cell (HSC) functioning. Such changes lead to aging-related hematopoietic/immune impairments and hematopoietic disorders. Understanding how such changes are initiated and how they progress will help in the development of medications that could improve the quality life for the elderly and to treat and possibly prevent aging-related hematopoietic diseases. Here, we review the most recent advances in research into HSC aging and discuss the role of HSC-intrinsic events, as well as those that relate to the aging bone marrow niche microenvironment in the overall processes of HSC aging. In addition, we discuss the potential mechanisms by which HSC aging is regulated.
Literature
3.
go back to reference Dale DC, Rosenberg PS, Alter BP. Lineage-specific hematopoietic growth factors. N Engl J Med. 2006;355:526–7.CrossRefPubMed Dale DC, Rosenberg PS, Alter BP. Lineage-specific hematopoietic growth factors. N Engl J Med. 2006;355:526–7.CrossRefPubMed
28.
go back to reference Liang Y, Van Zant G, Szilvassy SJ. Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood. 2005;106:1479–87.CrossRefPubMedPubMedCentral Liang Y, Van Zant G, Szilvassy SJ. Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood. 2005;106:1479–87.CrossRefPubMedPubMedCentral
30.
go back to reference Cho RH, Sieburg HB, Muller-Sieburg CE. 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. 2008;111:5553–61.CrossRefPubMedPubMedCentral Cho RH, Sieburg HB, Muller-Sieburg CE. 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. 2008;111:5553–61.CrossRefPubMedPubMedCentral
31.
go back to reference Beerman I, et al. Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc Natl Acad Sci U S A. 2011;107:5465–70.CrossRef Beerman I, et al. Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc Natl Acad Sci U S A. 2011;107:5465–70.CrossRef
36.
go back to reference Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol. 2004;5:133–9.CrossRefPubMed Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol. 2004;5:133–9.CrossRefPubMed
38.
go back to reference Suda T, Arai F, Hirao A. Hematopoietic stem cells and their niche. Trends Immunol. 2005;26:426–33.CrossRefPubMed Suda T, Arai F, Hirao A. Hematopoietic stem cells and their niche. Trends Immunol. 2005;26:426–33.CrossRefPubMed
42.
go back to reference Wilson A, et al. Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell. 2008;135:1118–29.CrossRefPubMed Wilson A, et al. Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell. 2008;135:1118–29.CrossRefPubMed
44.
go back to reference Okada S, et al. In vivo and in vitro stem cell function of c-kit- and Sca-1-positive murine hematopoietic cells. Blood. 1992;80:3044–50.CrossRefPubMed Okada S, et al. In vivo and in vitro stem cell function of c-kit- and Sca-1-positive murine hematopoietic cells. Blood. 1992;80:3044–50.CrossRefPubMed
45.
go back to reference Christensen JL, Weissman IL. Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells. Proc Natl Acad Sci U S A. 2001;98:14541–6.CrossRefPubMedPubMedCentral Christensen JL, Weissman IL. Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells. Proc Natl Acad Sci U S A. 2001;98:14541–6.CrossRefPubMedPubMedCentral
48.
go back to reference Kiel MJ, et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005;121:1109–21.CrossRefPubMed Kiel MJ, et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005;121:1109–21.CrossRefPubMed
51.
go back to reference Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996;183:1797–806.CrossRefPubMed Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996;183:1797–806.CrossRefPubMed
52.
go back to reference Challen GA, Boles NC, Chambers SM, Goodell MA. Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-beta1. Cell Stem Cell. 2010;6:265–78.CrossRefPubMedPubMedCentral Challen GA, Boles NC, Chambers SM, Goodell MA. Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-beta1. Cell Stem Cell. 2010;6:265–78.CrossRefPubMedPubMedCentral
61.
go back to reference Morrison SJ, Wandycz AM, Akashi K, Globerson A, Weissman IL. The aging of hematopoietic stem cells. Nat Med. 1996;2:1011–6.CrossRefPubMed Morrison SJ, Wandycz AM, Akashi K, Globerson A, Weissman IL. The aging of hematopoietic stem cells. Nat Med. 1996;2:1011–6.CrossRefPubMed
65.
75.
go back to reference Muller-Sieburg CE, Cho RH, Karlsson L, Huang JF, Sieburg HB. Myeloid-biased hematopoietic stem cells have extensive self-renewal capacity but generate diminished lymphoid progeny with impaired IL-7 responsiveness. Blood. 2004;103:4111–8.CrossRefPubMed Muller-Sieburg CE, Cho RH, Karlsson L, Huang JF, Sieburg HB. Myeloid-biased hematopoietic stem cells have extensive self-renewal capacity but generate diminished lymphoid progeny with impaired IL-7 responsiveness. Blood. 2004;103:4111–8.CrossRefPubMed
89.
go back to reference Cheshier SH, Morrison SJ, Liao X, Weissman IL. In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc Natl Acad Sci U S A. 1999;96:3120–5.CrossRefPubMedPubMedCentral Cheshier SH, Morrison SJ, Liao X, Weissman IL. In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc Natl Acad Sci U S A. 1999;96:3120–5.CrossRefPubMedPubMedCentral
90.
go back to reference Foudi A, et al. Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells. Nat Biotechnol. 2009;27:84–90.CrossRefPubMed Foudi A, et al. Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells. Nat Biotechnol. 2009;27:84–90.CrossRefPubMed
119.
go back to reference Dokal I, Vulliamy T. Inherited aplastic anaemias/bone marrow failure syndromes. Blood Rev. 2008;22:141–53.CrossRefPubMed Dokal I, Vulliamy T. Inherited aplastic anaemias/bone marrow failure syndromes. Blood Rev. 2008;22:141–53.CrossRefPubMed
129.
go back to reference Yalcin S, et al. Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells. J Biol Chem. 2008;283:25692–705.CrossRefPubMed Yalcin S, et al. Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells. J Biol Chem. 2008;283:25692–705.CrossRefPubMed
133.
go back to reference Chen C, et al. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J Exp Med. 2008;205:2397–408.CrossRefPubMedPubMedCentral Chen C, et al. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J Exp Med. 2008;205:2397–408.CrossRefPubMedPubMedCentral
147.
go back to reference Bennett-Baker PE, Wilkowski J, Burke DT. Age-associated activation of epigenetically repressed genes in the mouse. Genetics. 2003;165:2055–62.PubMedPubMedCentral Bennett-Baker PE, Wilkowski J, Burke DT. Age-associated activation of epigenetically repressed genes in the mouse. Genetics. 2003;165:2055–62.PubMedPubMedCentral
151.
go back to reference Park IK, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature. 2003;423:302–5.CrossRefPubMed Park IK, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature. 2003;423:302–5.CrossRefPubMed
158.
go back to reference Sen GL, Reuter JA, Webster DE, Zhu L, Khavari PA. DNMT1 maintains progenitor function in self-renewing somatic tissue. Nature. 2011;463:563–7.CrossRef Sen GL, Reuter JA, Webster DE, Zhu L, Khavari PA. DNMT1 maintains progenitor function in self-renewing somatic tissue. Nature. 2011;463:563–7.CrossRef
185.
go back to reference Adolfsson J, et al. Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell. 2005;121:295–306.CrossRefPubMed Adolfsson J, et al. Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell. 2005;121:295–306.CrossRefPubMed
192.
go back to reference Calvi LM, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841–6.CrossRefPubMed Calvi LM, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841–6.CrossRefPubMed
193.
go back to reference Zhang J, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425:836–41.CrossRefPubMed Zhang J, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425:836–41.CrossRefPubMed
231.
go back to reference Katayama Y, et al. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell. 2006;124:407–21.CrossRefPubMed Katayama Y, et al. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell. 2006;124:407–21.CrossRefPubMed
255.
go back to reference Butler JM, et al. Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. Cell Stem Cell. 2010;6:251–64.CrossRefPubMedPubMedCentral Butler JM, et al. Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. Cell Stem Cell. 2010;6:251–64.CrossRefPubMedPubMedCentral
256.
go back to reference Li W, et al. Primary endothelial cells isolated from the yolk sac and para-aortic splanchnopleura support the expansion of adult marrow stem cells in vitro. Blood. 2003;102:4345–53.CrossRefPubMed Li W, et al. Primary endothelial cells isolated from the yolk sac and para-aortic splanchnopleura support the expansion of adult marrow stem cells in vitro. Blood. 2003;102:4345–53.CrossRefPubMed
257.
go back to reference Li W, Johnson SA, Shelley WC, Yoder MC. Hematopoietic stem cell repopulating ability can be maintained in vitro by some primary endothelial cells. Exp Hematol. 2004;32:1226–37.CrossRefPubMed Li W, Johnson SA, Shelley WC, Yoder MC. Hematopoietic stem cell repopulating ability can be maintained in vitro by some primary endothelial cells. Exp Hematol. 2004;32:1226–37.CrossRefPubMed
258.
260.
go back to reference Kobayashi H, et al. Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells. Nat Cell Biol. 2010;12:1046–56.CrossRefPubMedPubMedCentral Kobayashi H, et al. Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells. Nat Cell Biol. 2010;12:1046–56.CrossRefPubMedPubMedCentral
264.
go back to reference Heissig B, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002;109:625–37.CrossRefPubMedPubMedCentral Heissig B, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002;109:625–37.CrossRefPubMedPubMedCentral
272.
go back to reference Sun L, et al. Angiopoietin-1 facilitates recovery of hematopoiesis in radiated mice. Am J Transl Res. 2016;8:2011–21.PubMedPubMedCentral Sun L, et al. Angiopoietin-1 facilitates recovery of hematopoiesis in radiated mice. Am J Transl Res. 2016;8:2011–21.PubMedPubMedCentral
276.
289.
go back to reference Visnjic D, et al. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood. 2004;103:3258–64.CrossRefPubMed Visnjic D, et al. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood. 2004;103:3258–64.CrossRefPubMed
294.
go back to reference Xing, Z. et al. Increased hematopoietic stem cell mobilization in aged mice. Blood (2006). Xing, Z. et al. Increased hematopoietic stem cell mobilization in aged mice. Blood (2006).
Metadata
Title
Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches
Authors
Lei Zhang
Ryan Mack
Peter Breslin
Jiwang Zhang
Publication date
01-12-2020
Publisher
BioMed Central
Keyword
Epigenetics
Published in
Journal of Hematology & Oncology / Issue 1/2020
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-020-00994-z

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