Skip to main content

Hematopoietic Stem Cell Repopulation After Transplantation: Role of Vinculin

  • Chapter
  • First Online:
Stem Cells and Cancer Stem Cells, Volume 2

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 2))

  • 1341 Accesses

Abstract

Hematopoietic stem cells (HSCs) are the most thoroughly characterized type of stem cells, and reconstitution of the hematopoietic system after HSC transplantation has demonstrated the self-renewal and differentiation capabilities of stem cells in vivo. HSCs must undergo several steps to achieve reconstitution after transplantation, e.g., homing to the bone marrow, lodging in the bone marrow niche, and proliferation and multilineage differentiation (repopulation). Identification of the factors required for HSCs to perform these reconstitution functions might improve our understanding of stem cell biology, as well as leading to more efficient HSC transplantation protocols. The gold standard for analyzing the function of target genes in HSCs is the creation of gene-deficient, knockout mice by gene targeting, while silencing of target gene expression by RNA interference is an attractive alternative strategy. In this chapter, we will explain the RNA interference methods available for silencing genes in HSCs using lentiviral vectors, and discuss the role of vinculin in HSC repopulation after transplantation.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

  • Chan JY, Watt SM (2001) Adhesion receptors on haematopoietic progenitor cells. Br J Haematol 112:541–557

    Article  PubMed  CAS  Google Scholar 

  • Coller BS, Shattil SJ (2008) The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend. Blood 112:3011–3025

    Article  PubMed  CAS  Google Scholar 

  • Cullen BR (2006) Induction of stable RNA interference in mammalian cells. Gene Ther 13:503–508

    Article  PubMed  CAS  Google Scholar 

  • Frecha C, Szecsi J, Cosset FL, Verhoeyen E (2008) Strategies for targeting lentiviral vectors. Curr Gene Ther 8:449–460

    Article  PubMed  CAS  Google Scholar 

  • Golebiewska A, Brons NH, Bjerkvig R, Niclou SP (2011) Critical appraisal of the side population assay in stem cell and cancer stem cell research. Cell Stem Cell 8:136–147

    Article  PubMed  CAS  Google Scholar 

  • Imai Y, Shimaoka M, Kurokawa M (2010) Essential roles of VLA-4 in the hematopoietic system. Int J Hematol 91:569–575

    Article  PubMed  Google Scholar 

  • Kiel MJ, Morrison SJ (2006) Maintaining hematopoietic stem cells in the vascular niche. Immunity 25:862–864

    Article  PubMed  CAS  Google Scholar 

  • Kohn DB (2008) Gene therapy for childhood immunological diseases. Bone Marrow Transplant 41:199–205

    Article  PubMed  CAS  Google Scholar 

  • Landry P, Plante I, Ouellet DL, Perron MP, Rousseau G, Provost P (2009) Existence of a microRNA pathway in anucleate platelets. Nat Struct Mol Biol 16:961–966

    Article  PubMed  CAS  Google Scholar 

  • Li J (2011) Quiescence regulators for hematopoietic stem cell. Exp Hematol 39:511–520

    Article  PubMed  Google Scholar 

  • Marg S, Winkler U, Sestu M, Himmel M, Schonherr M, Bar J, Mann A, Moser M, Mierke CT, Rottner K, Blessing M, Hirrlinger J, Ziegler WH (2010) The vinculin-DeltaIn20/21 mouse: characteristics of a constitutive, actin-binding deficient splice variant of vinculin. PLoS One 5:e11530

    Article  PubMed  Google Scholar 

  • Mitsios JV, Prevost N, Kasirer-Friede A, Gutierrez E, Groisman A, Abrams CS, Wang Y, Litvinov RI, Zemljic-Harpf A, Ross RS, Shattil SJ (2010) What is vinculin needed for in platelets? J Thromb Haemost 8:2294–2304

    Article  PubMed  CAS  Google Scholar 

  • Montini E, Cesana D, Schmidt M, Sanvito F, Bartholomae CC, Ranzani M, Benedicenti F, Sergi LS, Ambrosi A, Ponzoni M, Doglioni C, Di Serio C, von Kalle C, Naldini L (2009) The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy. J Clin Invest 119:964–975

    Article  PubMed  CAS  Google Scholar 

  • Moser M, Legate KR, Zent R, Fassler R (2009) The tail of integrins, talin, and kindlins. Science 324:895–899

    Article  PubMed  CAS  Google Scholar 

  • Nakauchi H, Sudo K, Ema H (2001) Quantitative assessment of the stem cell self-renewal capacity. Ann NY Acad Sci 938:18–24, discussion 24-15

    Article  PubMed  CAS  Google Scholar 

  • Nieswandt B, Moser M, Pleines I, Varga-Szabo D, Monkley S, Critchley D, Fassler R (2007) Loss of talin1 in platelets a brogates integrin activation, platelet aggregation, and thrombus formation in vitro and in vivo. J Exp Med 204:3113–3118

    Article  PubMed  CAS  Google Scholar 

  • Ogaeri T, Eto K, Otsu M, Ema H, Nakauchi H (2009) The actin polymerization regulator WAVE2 is required for early bone marrow repopulation by hematopoietic stem cells. Stem Cells 27:1120–1129

    Article  PubMed  CAS  Google Scholar 

  • Ohmori T, Kashiwakura Y, Ishiwata A, Madoiwa S, Mimuro J, Sakata Y (2007) Silencing of a targeted protein in in vivo platelets using a lentiviral vector delivering short hairpin RNA sequence. Arterioscler Thromb Vasc Biol 27:2266–2272

    Article  PubMed  CAS  Google Scholar 

  • Ohmori T, Kashiwakura Y, Ishiwata A, Madoiwa S, Mimuro J, Furukawa Y, Sakata Y (2010a) Vinculin is indispensable for repopulation by hematopoietic stem cells, independent of integrin function. J Biol Chem 285:31763–31773

    Article  PubMed  CAS  Google Scholar 

  • Ohmori T, Kashiwakura Y, Ishiwata A, Madoiwa S, Mimuro J, Honda S, Miyata T, Sakata Y (2010b) Vinculin activates inside-out signaling of integrin alphaIIbbeta3 in Chinese hamster ovary cells. Biochem Biophys Res Commun 400:323–328

    Article  PubMed  CAS  Google Scholar 

  • Peng X, Cuff LE, Lawton CD, DeMali KA (2010) Vinculin regulates cell-surface E-cadherin expression by binding to beta-catenin. J Cell Sci 123:567–577

    Article  PubMed  CAS  Google Scholar 

  • Petrich BG, Marchese P, Ruggeri ZM, Spiess S, Weichert RA, Ye F, Tiedt R, Skoda RC, Monkley SJ, Critchley DR, Ginsberg MH (2007) Talin is required for integrin-mediated platelet function in hemostasis and thrombosis. J Exp Med 204:3103–3111

    Article  PubMed  CAS  Google Scholar 

  • Rawls AS, Gregory AD, Woloszynek JR, Liu F, Link DC (2007) Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential. Blood 110:2414–2422

    Article  PubMed  CAS  Google Scholar 

  • Rubinson DA, Dillon CP, Kwiatkowski AV, Sievers C, Yang L, Kopinja J, Rooney DL, Ihrig MM, McManus MT, Gertler FB, Scott ML, Van Parijs L (2003) A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat Genet 33:401–406

    Article  PubMed  CAS  Google Scholar 

  • Srour EF, Jetmore A, Wolber FM, Plett PA, Abonour R, Yoder MC, Orschell-Traycoff CM (2001) Homing, cell cycle kinetics and fate of transplanted hematopoietic stem cells. Leukemia 15:1681–1684

    Article  PubMed  CAS  Google Scholar 

  • Takada Y, Ye X, Simon S (2007) The integrins. Genome Biol 8:215

    Article  PubMed  Google Scholar 

  • Wilson A, Trumpp A (2006) Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 6:93–106

    Article  PubMed  CAS  Google Scholar 

  • Yin T, Li L (2006) The stem cell niches in bone. J Clin Invest 116:1195–1201

    Article  PubMed  CAS  Google Scholar 

  • Yokota T, Oritani K, Mitsui H, Aoyama K, Ishikawa J, Sugahara H, Matsumura I, Tsai S, Tomiyama Y, Kanakura Y, Matsuzawa Y (1998) Growth-supporting activities of fibronectin on hematopoietic stem/progenitor cells in vitro and in vivo: structural requirement for fibronectin activities of CS1 and cell-binding domains. Blood 91:3263–3272

    PubMed  CAS  Google Scholar 

  • Ziegler WH, Liddington RC, Critchley DR (2006) The structure and regulation of vinculin. Trends Cell Biol 16:453–460

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tsukasa Ohmori .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Ohmori, T., Sakata, Y. (2012). Hematopoietic Stem Cell Repopulation After Transplantation: Role of Vinculin. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 2. Stem Cells and Cancer Stem Cells, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2016-9_11

Download citation

Publish with us

Policies and ethics