Skip to main content
SpringerLink
Log in

Aging of Murine Hematopoietic Stem Cells

  • Chapter
Stem Cell Aging: Mechanisms, Consequences, Rejuvenation

  • 1163 Accesses

Abstract

Hematopoietic stem cells (HSCs) are unique in their ability to self-renew and differentiate into all mature blood lineages. The equilibrium between these processes is crucial for tissue maintenance during the lifetime of the organism. However, with age the functionality of HSCs declines, resulting in development of anemias, deficiencies of immune response, and increased risk of hematopoietic malignancies. Aged HSCs are characterized by preferential differentiation toward myeloid lineage, impaired self-renewal, and engraftment. Recent evidence provides clues to the understanding of these processes on cellular and molecular levels. Key components contributing to stem cell aging are shifts in the transcriptome and epigenome, accompanied by dysfunction of DNA repair pathways. In this chapter we will focus on studies and conceptual models of murine HSC aging.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Arai F, Suda T (2007) Maintenance of quiescent hematopoietic stem cells in the osteoblastic niche. Ann N Y Acad Sci 1106:41–53

    Article  CAS  PubMed  Google Scholar 

  • Attema JL, Pronk CJ, Norddahl GL, Nygren JM, Bryder D (2009) Hematopoietic stem cell ageing is uncoupled from p16 INK4A-mediated senescence. Oncogene 28(22):2238–2243

    Article  CAS  PubMed  Google Scholar 

  • Balducci L, Ershler W, Gaetano G (eds) (2008) Blood disorders in the elderly. Cambridge University Press, New York

    Google Scholar 

  • Beerman I, Bhattacharya D, Zandi S, Sigvardsson M, Weissman IL, Bryder D et al (2010a) Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc Natl Acad Sci U S A 107(12):5465–5470

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Beerman I, Maloney WJ, Weissmann IL, Rossi DJ (2010b) Stem cells and the aging hematopoietic system. Curr Opin Immunol 22(4):500–506

    Article  CAS  PubMed  Google Scholar 

  • Beerman I, Bock C, Garrison BS, Smith ZD, Gu H, Meissner A et al (2013) Proliferation- dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging. Cell Stem Cell 12:413–425

    Article  CAS  PubMed  Google Scholar 

  • Benz C, Copley MR, Kent DG, Wohrer S, Cortes A, Aghaeepour N et al (2012) Hematopoietic stem cell subtypes expand differentially during development and display distinct lymphopoietic programs. Cell Stem Cell 10(3):273–283

    Article  CAS  PubMed  Google Scholar 

  • Bertoncello I, Hodgson GS, Bradley TR (1985) Multiparameter analysis of transplantable hemopoietic stem cells: I. The separation and enrichment of stem cells homing to marrow and spleen on the basis of rhodamine-123 fluorescence. Exp Hematol 13(10):999–1006

    CAS  PubMed  Google Scholar 

  • Blanpain C, Mohrin M, Sotiropoulou PA, Passegue E (2011) DNA-damage response in tissue- specific and cancer stem cells. Cell Stem Cell 8(1):16–29

    Article  CAS  PubMed  Google Scholar 

  • Boon RA, Iekushi K, Lechner S, Seeger T, Fischer A, Heydt S et al (2013) MicroRNA-34a regulates cardiac ageing and function. Nature 495:107–110

    Article  CAS  PubMed  Google Scholar 

  • Bruunsgaard H, Pedersen AN, Schroll M, Skinhoj P, Pedersen BK (1999) Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly humans. Clin Exp Immunol 118(2):235–241

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Challen GA, Boles N, Lin KK, Goodell MA (2009) Mouse hematopoietic stem cell identification and analysis. Cytometry A 75(1):14–24

    Article  PubMed Central  PubMed  Google Scholar 

  • Challen GA, Boles NC, Chambers SM, Goodell MA (2010) Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-beta1. Cell Stem Cell 6(3):265–278

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chambers SM, Shaw CA, Gatza C, Fisk CJ, Donehower LA, Goodell MA (2007a) Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biol 5(8), e201

    Article  PubMed Central  PubMed  Google Scholar 

  • Chambers SM, Boles NC, Lin KY, Tierney MP, Bowman TV, Bradfute SB et al (2007b) Hematopoietic fingerprints: an expression database of stem cells and their progeny. Cell Stem Cell 1(5):578–591

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen C, Liu Y, Liu Y, Zheng P (2009) mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal 2(98):ra75

    Article  PubMed Central  PubMed  Google Scholar 

  • Cheshier SH, Morrison SJ, Liao X, Weissman IL (1999) In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc Natl Acad Sci U S A 96(6):3120–3125

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cho RH, Sieburg HB, Muller-Sieburg CE (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 111(12):5553–5561

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Di Micco R, Sulli G, Dobreva M, Liontos M, Botrugno OA, Gargiulo G et al (2011) Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer. Nat Cell Biol 13(3):292–302

    Article  PubMed Central  PubMed  Google Scholar 

  • Dykstra B, de Haan G (2008) Hematopoietic stem cell aging and self-renewal. Cell Tissue Res 331(1):91–101

    Article  PubMed  Google Scholar 

  • Dykstra B, Ramunas J, Kent D, McCaffrey L, Szumsky E, Kelly L et al (2006) High-resolution video monitoring of hematopoietic stem cells cultured in single-cell arrays identifies new features of self-renewal. Proc Natl Acad Sci U S A 103(21):8185–8190

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dykstra B, Kent D, Bowie M, McCaffrey L, Hamilton M, Lyons K et al (2007) Long-term propagation of distinct hematopoietic differentiation programs in vivo. Cell Stem Cell 1(2):218–229

    Article  CAS  PubMed  Google Scholar 

  • Dykstra B, Olthof S, Schreuder J, Ritsema M, de Haan G (2011) Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells. J Exp Med 208(13):2691–2703

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ema H, Sudo K, Seita J, Matsubara A, Morita Y, Osawa M et al (2005) Quantification of self- renewal capacity in single hematopoietic stem cells from normal and Lnk-deficient mice. Dev Cell 8(6):907–914

    Article  CAS  PubMed  Google Scholar 

  • Ergen AV, Boles NC, Goodell MA (2012) Rantes/Ccl5 influences hematopoietic stem cell subtypes and causes myeloid skewing. Blood 119(11):2500–2509

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ershler WB, Keller ET (2000) Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med 51:245–270

    Article  CAS  PubMed  Google Scholar 

  • Flach J, Bakker ST, Mohrin M, Conroy PC, Pietras EM et al (2014) Replicative stress is a potent driver of functional decline in ageing hematopoietic stem cells. Nature 512(7513):198–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Florian MC, Dorr K, Niebel A, Daria D, Schrezenmeier H, Rojewski M et al (2012) Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell Stem Cell 10(5):520–530

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Florian CM, Nattamai KJ, Doerr K, Marka G, Überle B et al (2013) A canonical to non-canonical Wnt signaling switch in hematopoietic stem-cell ageing. Nature 503(7476):392–396

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Folmes CD, Dzeja PP, Nelson TJ, Terzic A (2012) Metabolic plasticity in stem cell homeostasis and differentiation. Cell Stem Cell 11(5):596–606

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Foudi A, Hochedlinger K, Van Buren D, Schindler JW, Jaenisch R, Carey V et al (2009) Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells. Nat Biotechnol 27(1):84–90

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183(4):1797–1806

    Article  CAS  PubMed  Google Scholar 

  • Goodman JW, Hodgson GS (1962) Evidence for stem cells in the peripheral blood of mice. Blood 19:702–714

    CAS  PubMed  Google Scholar 

  • Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11(3):298–300

    Article  CAS  PubMed  Google Scholar 

  • Harrison DE (1983) Long-term erythropoietic repopulating ability of old, young, and fetal stem cells. J Exp Med 157(5):1496–1504

    Article  CAS  PubMed  Google Scholar 

  • Harrison DE, Astle CM, Stone M (1989) Numbers and functions of transplantable primitive immunohematopoietic stem cells. Effects of age. J Immunol 142(11):3833–3840

    CAS  PubMed  Google Scholar 

  • Hidalgo I, Herrera-Merchan A, Ligos JM, Carramolino L, Nunez J, Martinez F et al (2012) Ezh1 is required for hematopoietic stem cell maintenance and prevents senescence-like cell cycle arrest. Cell Stem Cell 11(5):649–662

    Article  CAS  PubMed  Google Scholar 

  • Hilpert M, Legrand C, Bluteau C, Balayn N, Betems A et al (2014) p19 INK4d controls hematopoietic stem cell in a cell-autonomous manner during genotoxic stress and through the microenvironment during aging. Stem Cell Reports 3(6):1085–1102

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I et al (2004) Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 431(7011):997–1002

    Article  CAS  PubMed  Google Scholar 

  • Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K et al (2006) Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med 12(4):446–451

    Article  CAS  PubMed  Google Scholar 

  • Jang YY, Sharkis SJ (2007) A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood 110(8):3056–3063

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM et al (2006) Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443(7110):421–426

    CAS  PubMed  Google Scholar 

  • Jordan CT, Lemischka IR (1990) Clonal and systemic analysis of long-term hematopoiesis in the mouse. Genes Dev 4(2):220–232

    Article  CAS  PubMed  Google Scholar 

  • Ju Z, Jiang H, Jaworski M, Rathinam C, Gompf A, Klein C et al (2007) Telomere dysfunction induces environmental alterations limiting hematopoietic stem cell function and engraftment. Nat Med 13(6):742–747

    Article  CAS  PubMed  Google Scholar 

  • Kamminga LM, van Os R, Ausema A, Noach EJ, Weersing E, Dontje B et al (2005) Impaired hematopoietic stem cell functioning after serial transplantation and during normal aging. Stem Cells 23(1):82–92

    Article  CAS  PubMed  Google Scholar 

  • Karin M, Ben-Neriah Y (2000) Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol 18:621–663

    Article  CAS  PubMed  Google Scholar 

  • Kent DG, Copley MR, Benz C, Wohrer S, Dykstra BJ, Ma E et al (2009) Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential. Blood 113(25):6342–6350

    Article  CAS  PubMed  Google Scholar 

  • Kiel MJ, Yilmaz OH, Iwashita T, Yilmaz OH, Terhorst C, Morrison SJ (2005) SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121(7):1109–1121

    Article  CAS  PubMed  Google Scholar 

  • Klebanov S, Flurkey K, Roderick TH, Archer JR, Astle MC, Chen J et al (2000) Heritability of life span in mice and its implication for direct and indirect selection for longevity. Genetica 110(3):209–218

    Article  CAS  PubMed  Google Scholar 

  • Kohler A, Schmithorst V, Filippi MD, Ryan MA, Daria D et al (2009) Altered cellular dynamics and endosteal location of aged early hematopoietic progenitor cells revealed by time-lapse intravital imaging in long bones. Blood 114(2):290–298

    Article  PubMed Central  PubMed  Google Scholar 

  • Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L et al (2004) Ink4a/Arf expression is a biomarker of aging. J Clin Invest 114(9):1299–1307

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lansdorp PM (1998) Stem cell biology for the transfusionist. Vox Sang 74(Suppl 2):91–94

    Article  CAS  PubMed  Google Scholar 

  • Liang Y, Van Zant G, Szilvassy SJ (2005) Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood 106(4):1479–1487

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Luo M, Jeong M, Sun D, Jung Park H, Rodrigues BAT et al (2015) Long non-coding RNAs control hematopoietic stem cell function. Cell Stem Cell 16(4):426–438

    Article  CAS  PubMed  Google Scholar 

  • Maryanovich M, Oberkovitz G, Niv H, Vorobiyov L, Zaltsman Y, Brenner O et al (2012) The ATM-BID pathway regulates quiescence and survival of haematopoietic stem cells. Nat Cell Biol 14(5):535–541

    Article  CAS  PubMed  Google Scholar 

  • Miller CL, Eaves CJ (1997) Expansion in vitro of adult murine hematopoietic stem cells with transplantable lympho-myeloid reconstituting ability. Proc Natl Acad Sci U S A 94(25):13648–13653

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mohrin M, Shin J, Liu Y, Brown K, Luo H et al (2015) A mitochondrial UPR-mediated checkpoint regulates hematopoietic stem cell aging. Science 347(6228):1347–1377

    Article  Google Scholar 

  • Morita Y, Ema H, Nakauchi H (2010) Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J Exp Med 207(6):1173–1182

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Morrison SJ, Wandycz AM, Akashi K, Globerson A, Weissman IL (1996) The aging of hematopoietic stem cells. Nat Med 2(9):1011–1016

    Article  CAS  PubMed  Google Scholar 

  • Muller-Sieburg C, Sieburg HB (2008) Stem cell aging: survival of the laziest? Cell Cycle 7(24):3798–3804

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Muller-Sieburg CE, Cho RH, Thoman M, Adkins B, Sieburg HB (2002) Deterministic regulation of hematopoietic stem cell self-renewal and differentiation. Blood 100(4):1302–1309

    CAS  PubMed  Google Scholar 

  • Muller-Sieburg CE, Cho RH, Karlsson L, Huang JF, Sieburg HB (2004) Myeloid-biased hematopoietic stem cells have extensive self-renewal capacity but generate diminished lymphoid progeny with impaired IL-7 responsiveness. Blood 103(11):4111–4118

    Article  CAS  PubMed  Google Scholar 

  • Nijnik A, Woodbine L, Marchetti C, Dawson S, Lambe T, Liu C et al (2007) DNA repair is limiting for haematopoietic stem cells during ageing. Nature 447(7145):686–690

    Article  CAS  PubMed  Google Scholar 

  • Noda S, Ichikawa H, Miyoshi H (2009) Hematopoietic stem cell aging is associated with functional decline and delayed cell cycle progression. Biochem Biophys Res Commun 383(2):210–215

    Article  CAS  PubMed  Google Scholar 

  • Norddahl GL, Pronk CJ, Wahlestedt M, Sten G, Nygren JM, Ugale A et al (2011) Accumulating mitochondrial DNA mutations drive premature hematopoietic aging phenotypes distinct from physiological stem cell aging. Cell Stem Cell 8(5):499–510

    Article  CAS  PubMed  Google Scholar 

  • Orford KW, Scadden DT (2008) Deconstructing stem cell self-renewal: genetic insights into cell- cycle regulation. Nat Rev Genet 9(2):115–128

    Article  CAS  PubMed  Google Scholar 

  • Parmar K, Mauch P, Vergilio JA, Sackstein R, Down JD (2007) Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc Natl Acad Sci U S A 104(13):5431–5436

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Passegue E, Wagers AJ, Giuriato S, Anderson WC, Weissman IL (2005) Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates. J Exp Med 202(11):1599–1611

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ramshaw HS, Crittenden RB, Dooner M, Peters SO, Rao SS, Quesenberry PJ (1995) High levels of engraftment with a single infusion of bone marrow cells into normal unprepared mice. Biol Blood Marrow Transplant 1(2):74–80

    CAS  PubMed  Google Scholar 

  • Rossi DJ, Bryder D, Zahn JM, Ahlenius H, Sonu R, Wagers AJ et al (2005) Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc Natl Acad Sci U S A 102(26):9194–9199

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rossi DJ, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman IL (2007) Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature 447(7145):725–729

    Article  CAS  PubMed  Google Scholar 

  • Salih DA, Brunet A (2008) FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr Opin Cell Biol 20(2):126–136

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Simsek T, Kocabas F, Zheng J, Deberardinis RJ, Mahmoud AI, Olson EN et al (2010) The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell 7(3):380–390

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sudo K, Ema H, Morita Y, Nakauchi H (2000) Age-associated characteristics of murine hematopoietic stem cells. J Exp Med 192(9):1273–1280

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sun D, Luo M, Jeong M, Rodriguez B, Xia Z et al (2014) Epigenomic profiling of young and aged HSCs reveals concerted changes that reinforces self-renewal. Cell Stem Cell 14(5):673–688

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Takizawa H, Regoes RR, Boddupalli CS, Bonhoeffer S, Manz MG (2011) Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammation. J Exp Med 208(2):273–284

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Takubo K, Goda N, Yamada W, Iriuchishima H, Ikeda E, Kubota Y et al (2010) Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell 7(3):391–402

    Article  CAS  PubMed  Google Scholar 

  • Tothova Z, Kollipara R, Huntly BJ, Lee BH, Castrillon DH, Cullen DE et al (2007) FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 128(2):325–339

    Article  CAS  PubMed  Google Scholar 

  • van Os R, Ausema A, Dontje B, van Riezen M, van Dam G, de Haan G (2010) Engraftment of syngeneic bone marrow is not more efficient after intrafemoral transplantation than after traditional intravenous administration. Exp Hematol 38(11):1115–1123

    Article  PubMed  Google Scholar 

  • Verovskaya EV, de Haan G (2011) The power of diversity: hematopoietic stem cell heterogeneity and its clinical relevance. Hematol Educ 5(1):132–139

    Google Scholar 

  • Verovskaya E, Broekhuis MJC, Zwart E, Ritsema M, van Os R et al (2013) Heterogeneity of young and aged murine hematopoietic stem cells revealed by quantitative clonal analysis using cellular barcoding. Blood 122(4):523–532

    Article  CAS  PubMed  Google Scholar 

  • Verovskaya E, Broekhuis MJC, Zwart E, Weersing E, Ritsema M, Bosman LJ et al (2014) Asymmetry in skeletal distribution of mouse hematopoietic stem cell clones and their equilibration by mobilizing cytokines. J Exp Med 211(3):487–497

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wang J, Sun Q, Morita Y, Jiang H, Gross A, Lechel A et al (2012) A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage. Cell 148(5):1001–1014

    Article  CAS  PubMed  Google Scholar 

  • Warr MR, Binnewies M, Flach J, Reynaud D, Garg T et al (2013) FOXO3A directs a protective autophagy in hematopoietic stem cells. Nature 494(7437):323–327

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wilson A, Laurenti E, Oser G, van der Wath RC, Blanco-Bose W, Jaworski M et al (2008) Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell 135(6):1118–1129

    Article  CAS  PubMed  Google Scholar 

  • Wolf NS, Kone A, Priestley GV, Bartelmez SH (1993) In vivo and in vitro characterization of long- term repopulating primitive hematopoietic cells isolated by sequential Hoechst 33342-rhodamine123 FACS selection. Exp Hematol 21(5):614–622

    CAS  PubMed  Google Scholar 

  • Wright DE, Wagers AJ, Gulati AP, Johnson FL, Weissman IL (2001) Physiological migration of hematopoietic stem and progenitor cells. Science 294(5548):1933–1936

    Article  CAS  PubMed  Google Scholar 

  • Xing Z, Ryan MA, Daria D, Nattamai KJ, Van Zant G, Wang L et al (2006) Increased hematopoietic stem cell mobilization in aged mice. Blood 108(7):2190–2197

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yilmaz OH, Kiel MJ, Morrison SJ (2006) SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity. Blood 107(3):924–930

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ et al (2001) The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 7(9):1028–1034

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Netherlands Institute for Regenerative Medicine (NIRM), the European Union FP7 Marie Curie Initial Training Network “EuroCancer Stem Cell Training,” the Netherlands Organization for Scientific Research (NWO), and the Mouse Clinic for Cancer and Aging, part of the large RoadMap Initiatives funded by the Dutch Ministry of Education, Culture, and Science.

Author information

Authors and Affiliations

  1. Department of Ageing Biology and Stem Cells, European Research Institute for the Biology of Aging (ERIBA), University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands

    Edyta Wόjtowicz, Evgenia Verovskaya & Gerald de Haan

Authors
  1. Edyta Wόjtowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evgenia Verovskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gerald de Haan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gerald de Haan .

Editor information

Editors and Affiliations

  1. Dermatology and Allergic Diseases, Ulm University, Ulm, Germany

    Hartmut Geiger

  2. Department of Biology, University of Rochester, Rochester, New York, USA

    Heinrich Jasper

  3. Dermatology and Allergic Diseases, Ulm University, Ulm, Germany

    Maria Carolina Florian

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Wien

About this chapter

Cite this chapter

Wόjtowicz, E., Verovskaya, E., de Haan, G. (2015). Aging of Murine Hematopoietic Stem Cells. In: Geiger, H., Jasper, H., Florian, M. (eds) Stem Cell Aging: Mechanisms, Consequences, Rejuvenation. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1232-8_6

Download citation

Publish with us

Policies and ethics

Search

Navigation