Skip to main content

Regulation of Hematopoietic Stem Cells in the Osteoblastic Niche

  • Conference paper
Osteoimmunology

Part of the book series: Advances in Experimental Medicine and Biology ((volume 602))

Tissue stem cells are characterized by their abilities to self-renew and to produce numerous differentiated daughter cells. These two special properties enable stem cells to play a central role in maintaining tissues. Many adult tissue stem cells, including hematopoietic system, skin epidermis, gastrointestinal epithelium, brain, and lung were identified (Fuchs, Tumbar, and Guasch 2004; Moore and Lemischka 2006). The activity of tissue stem cells is crucial for supplying the mature cells in normal tissue turnover. It now clear that the stem cell niche regulates the stem cell-specific properties, including self-renewal activity, multi-potentiality, and relative quiescence (Suda, Arai, and Hirao 2005; Adams and Scadden 2006; Wilson and Trumpp 2006). Interaction of stem cells with stem cell niches is critical for maintaining the stem cell properties, including self-renewal capacity and the ability of differentiation into single or multiple lineages.

Hematopoietic stem cells (HSCs) are responsible for blood cell production throughout the lifetime of individual. BM HSCs are best-characterized stem cells. A small subset of HSCs is isolated by cell surface markers (Spangrude, Heimfeld, and Weissman 1988; Osawa, Hanada, Hamada, et al. 1996). These HSCs differentiate into myeloid cells, B cells, and T cells in the presence of various cytokines (Akashi, Traver, Miyamoto, and Weissman 2000). It has been reported that single purified HSC is able to reconstitute lethally irradiated mice (Osawa, Hanada, Hamada, et al.; Matsuzaki, Kinjo, Mulligan, et al. 2004). In contrast to the identification of HSCs, the localization of HSCs in situ and structure of HSC niche had not been solved. Recently, long-term bone marrow (BM) repopulating (LTR) HSCs have been found in BM trabecular bone surface, and it was clarified that an osteoblastic (OB) cell is a critical component for sustaining HSCs (Calvi, Adams, Weibrecht, et al. 2003; Zhang, Niu, Ye, et al. 2003). Long-term label retaining cell (LRC) study showed that 89 % of CD45+Lin- LRCs attached to the endosteal surface (Zhang, Niu, Ye, et al. 2003). It suggests that quiescent/slow-dividing HSCs exclusively located in the osteoblastic niche. HSCs keep a balance between quiescence and cell division/proliferation in the osteoblastic niche (Arai, Hirao, Ohmura, et al. 2004). The specific properties of HSC are controlled dynamically by the signalings of receptor/ligand and cell adhesion molecules produced by osteoblastic niche cells (Suda, Arai, and Hirao 2005; Wilson and Trumpp 2006).

We described here the characterization of HSC and their niche, and the environmental regulation of HSCs in the niche.

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 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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adams, G.B., and D.T. Scadden. 2006. The hematopoietic stem cell in its place. Nat Immunol 7(4): 333–337.

    Article  CAS  PubMed  Google Scholar 

  2. Akashi, K., D. Traver, T. Miyamoto, and I.L. Weissman. 2000. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404(6774): 193–197.

    Article  CAS  PubMed  Google Scholar 

  3. Allsopp, R.C., G.B. Morin, R. DePinho, C.B. Harley, and I.L. Weissman. 2003. Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation. Blood 102(2): 517–520.

    Article  CAS  PubMed  Google Scholar 

  4. Arai, F., O. Ohneda, T. Miyamoto, X.Q. Zhang, and T. Suda. 2002. Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation. J Exp Med 195(12): 1549–1563.

    Article  CAS  PubMed  Google Scholar 

  5. Arai, F., A. Hirao, M. Ohmura, H. Sato, S. Matsuoka, K. Takubo, K. Ito, G.Y. Koh, and T. Suda. 2004. Tie2/Angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118(2): 149–161.

    Article  CAS  PubMed  Google Scholar 

  6. Blanpain, C., W.E. Lowry, A. Geoghegan, L. Polak, and E. Fuchs. 2004. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell 118(5): 635–648.

    Article  CAS  PubMed  Google Scholar 

  7. Calvi, L.M., G.B. Adams, K.W. Weibrecht, J.M. Weber, D.P. Olson, M.C. Knight, R.P. Martin, E. Schipani, P. Divieti, F.R. Bringhurst, L.A. Milner, H.M. Kronenberg, and D.T. Scadden. 2003. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425(6960): 841–846.

    Article  CAS  PubMed  Google Scholar 

  8. Cheng, T., N. Rodrigues, H. Shen, Y. Yang, D. Dombkowski, M. Sykes, and D.T. Scadden. 2000. Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 287(5459): 1804–1808.

    Article  CAS  PubMed  Google Scholar 

  9. Davis, S., T.H. Aldrich, P.F. Jones, A. Acheson, D.L. Compton, V. Jain, T.E. Ryan, J. Bruno, C. Radziejewski, P.C. Maisonpierre, and G.D. Yancopoulos. 1996. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 87(7): 1161–1169.

    Article  CAS  PubMed  Google Scholar 

  10. Dumont, D.J., T.P. Yamaguchi, R.A. Conlon, J. Rossant, and M.L. Breitman. 1992. tek, a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors. Oncogene 7(8): 1471–1480.

    CAS  PubMed  Google Scholar 

  11. Dumont, D.J., G. Gradwohl, G.H. Fong, M.C. Puri, M. Gertsenstein, A. Auerbach, and M.L. Breitman. 1994. Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. Genes Dev 8(16): 1897–1909.

    Article  CAS  PubMed  Google Scholar 

  12. Ema, H., H. Takano, K. Sudo, and H. Nakauchi. 2000. In vitro self-renewal division of hematopoietic stem cells. J Exp Med 192(9): 1281–1288.

    Article  CAS  PubMed  Google Scholar 

  13. Fuchs, E., T. Tumbar, and G. Guasch. 2004. Socializing with the neighbors: stem cells and their niche. Cell 116(6): 769–778.

    Article  CAS  PubMed  Google Scholar 

  14. Goodell, M.A., K. Brose, G. Paradis, A.S. Conner, and R.C. Mulligan. 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 

  15. Goodell, M.A., M. Rosenzweig, H. Kim, D.F. Marks, M. DeMaria, G. Paradis, S.A. Grupp, C.A. Sieff, R.C. Mulligan, and R.P. Johnson. 1997. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med 3(12): 1337–1345.

    Article  CAS  PubMed  Google Scholar 

  16. Hüttmann, A., S.L. Liu, A.W. Boyd, and C.L. Li. 2001. Functional heterogeneity within rhodamine123(lo) Hoechst33342(lo/sp) primitive hemopoietic stem cells revealed by pyronin Y. Exp Hematol 29(9): 1109–1116.

    Article  PubMed  Google Scholar 

  17. Ito, K., A. Hirao, F. Arai, S. Matsuoka, K. Takubo, I. Hamaguchi, K. Nomiyama, K. Hosokawa, K. Sakurada, N. Nakagata, Y. Ikeda, T.W. Mak, and T. Suda. 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 

  18. Ito, K., A. Hirao, F. Arai, K. Takubo, S. Matsuoka, K. Miyamoto, M. Ohmura, K. Naka, K. Hosokawa, Y. Ikeda, and T. Suda. 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 

  19. Iwama, A., I. Hamaguchi, M. Hashiyama, Y. Murayama, K. Yasunaga, and T. Suda. 1993. Molecular cloning and characterization of mouse TIE and TEK receptor tyrosine kinase genes and their expression in hematopoietic stem cells. Biochem Biophys Res Commun 195(1): 301–309.

    Article  CAS  PubMed  Google Scholar 

  20. Kapuscinski, J., and Z. Darzynkiewicz. 1987. Interactions of pyronin Y(G) with nucleic acids. Cytometry 8(2): 129–137.

    Article  CAS  PubMed  Google Scholar 

  21. Lin, H. 2002. The stem-cell niche theory: lessons from flies. Nat Rev Genet 3(12): 931–940.

    Article  CAS  PubMed  Google Scholar 

  22. Matsuzaki, Y., K. Kinjo, R.C. Mulligan, and H. Okano. 2004. Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells. Immunity 20(1): 87–93.

    Article  CAS  PubMed  Google Scholar 

  23. Moore, K.A., and I.R. Lemischka. 2006. Stem cells and their niches. Science 311(5769): 1880–1885.

    Article  CAS  PubMed  Google Scholar 

  24. Murphy, M.J., A. Wilson, and A. Trumpp. 2005. More than just proliferation: Myc function in stem cells. Trends Cell Biol 15(3): 128–137.

    Article  CAS  PubMed  Google Scholar 

  25. Nilsson, S.K., H.M. Johnston, and J.A. Coverdale. 2001. Spatial localization of transplanted hemopoietic stem cells: inferences for the localization of stem cell niches. Blood 97(8): 2293–2299.

    Article  CAS  PubMed  Google Scholar 

  26. Osawa, M., K. Hanada, H. Hamada, and H. Nakauchi. 1996. Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 273(5272): 242–245.

    Article  CAS  PubMed  Google Scholar 

  27. Partanen, J., E. Armstrong, T.P. Makela, J. Korhonen, M. Sandberg, R. Renkonen, S. Knuutila, K. Huebner, and K. Alitalo. 1992. A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains. Mol Cell Biol 12(4): 1698–1707.

    CAS  PubMed  Google Scholar 

  28. Partanen, J., M.C. Puri, L. Schwartz, K.D. Fischer, A. Bernstein, and J. Rossant. 1996. Cell autonomous functions of the receptor tyrosine kinase TIE in a late phase of angiogenic capillary growth and endothelial cell survival during murine development. Development 122(10): 3013–3021.

    CAS  PubMed  Google Scholar 

  29. Puri, M.C., and A. Bernstein. 2003. Requirement for the TIE family of receptor tyrosine kinases in adult but not fetal hematopoiesis. Proc Natl Acad Sci USA 100(22): 12753–12758.

    Article  CAS  PubMed  Google Scholar 

  30. Rodewald, H.R., and T.N. Sato. 1996. Tie1 a receptor tyrosine kinase essential for vascular endothelial cell integrity, is not critical for the development of hematopoietic cells. Oncogene 12(2): 397–404.

    CAS  PubMed  Google Scholar 

  31. Sato, T.N., Y. Tozawa, U. Deutsch, K. Wolburg-Buchholz, Y. Fujiwara, M. Gendron-Maguire, T. Gridley, H. Wolburg, W. Risau, and Y. Qin. 1995. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature 376(6535): 70–74.

    Article  CAS  PubMed  Google Scholar 

  32. Sato, A., A. Iwama, N. Takakura, H. Nishio, G.D. Yancopoulos, and T. Suda. 1998. Characterization of TEK receptor tyrosine kinase and its ligands, angiopoietins, in human hematopoietic progenitor cells. Int Immunol 10(8): 1217–1227.

    Article  CAS  PubMed  Google Scholar 

  33. Schofield, R. 1978. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4(1–2): 7–25.

    CAS  PubMed  Google Scholar 

  34. Spangrude, G.J., S. Heimfeld, and I.L. Weissman. 1988. Purification and characterization of mouse hematopoietic stem cells. Science 241(4861): 58–62.

    Article  CAS  PubMed  Google Scholar 

  35. Suda, T., F. Arai, and A. Hirao. 2005. Hematopoietic stem cells and their niche. Trends Immunol 26(8): 426–433.

    Article  CAS  PubMed  Google Scholar 

  36. Suri, C., P.F. Jones, S. Patan, S. Bartunkova, P.C. Maisonpierre, S. Davis, T.N. Sato, and G.D. Yancopoulos. 1996. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87(7): 1171–1180.

    Article  CAS  PubMed  Google Scholar 

  37. Takakura, N., X.L. Huang, T. Naruse, I. Hamaguchi, D.J. Dumont, G.D. Yancopoulos, and T. Suda. 1998. Critical role of the TIE2 endothelial cell receptor in the development of definitive hematopoiesis. Immunity 9(5): 677–686.

    Article  CAS  PubMed  Google Scholar 

  38. Taichman, R.S., and S.G. Emerson. 1998. The role of osteoblasts in the hematopoietic microenvironment. Stem Cells 16(1): 7–15.

    Article  CAS  PubMed  Google Scholar 

  39. Tumbar, T., G. Guasch, V. Greco, C. Blanpain, W.E. Lowry, M. Rendl, and E. Fuchs. 2004. Defining the epithelial stem cell niche in skin. Science 303(5656): 359–363.

    Article  CAS  PubMed  Google Scholar 

  40. Vikkula, M., L.M. Boon, K.L. Carraway, 3rd, J.T. Calvert, A.J. Diamonti, B. Goumnerov, K.A. Pasyk, D.A. Marchuk, M.L. Warman, L.C. Cantley, J.B. Mulliken, and B.R. Olsen. 1996. Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2. Cell 87(7): 1181–1190.

    Article  CAS  PubMed  Google Scholar 

  41. Visnjic, D., Z. Kalajzic, D.W. Rowe, V. Katavic, J. Lorenzo, and H.L. Aguila. 2004. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood 103(9): 3258–3264.

    Article  CAS  PubMed  Google Scholar 

  42. Wilson, A., and A. Trumpp. 2006. Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 6(2): 93–106.

    Article  CAS  PubMed  Google Scholar 

  43. Wilson, A., M.J. Murphy, T. Oskarsson, K. Kaloulis, M.D. Bettess, G.M. Oser, A.C. Pasche, C. Knabenhans, H.R. Macdonald, and A. Trumpp. 2004. c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev 18(22): 2747–2763.

    Article  CAS  PubMed  Google Scholar 

  44. Wu, S., C. Cetinkaya, M.J. Munoz-Alonso, N. von der Lehr, F. Bahram, V. Beuger, M. Eilers, J. Leon, and L.G. Larsson. 2003. Myc represses differentiation-induced p21CIP1 expression via Miz-1-dependent interaction with the p21 core promoter. Oncogene 22(3): 351–360.

    Article  CAS  PubMed  Google Scholar 

  45. Yamashita, Y.M., D.L. Jones, and M.T. Fuller. 2003. Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science 301(5639): 1547–1550.

    Article  CAS  PubMed  Google Scholar 

  46. Zhang, J., C. Niu, L. Ye, H. Huang, X. He, W.G. Tong, J. Ross, J. Haug, T. Johnson, J.Q. Feng, S. Harris, L.M. Wiedemann, Y. Mishina, and L. Li. 2003. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425(6960): 836–841.

    Article  CAS  PubMed  Google Scholar 

  47. Zhou, S., J.D. Schuetz, K.D. Bunting, A.M. Colapietro, J. Sampath, J.J. Morris, I. Lagutina, G.C. Grosveld, M. Osawa, H. Nakauchi, and B.P. Sorrentino. 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

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer Science+Business Media, LLC

About this paper

Cite this paper

Aria, F., Suda, T. (2007). Regulation of Hematopoietic Stem Cells in the Osteoblastic Niche. In: Choi, Y. (eds) Osteoimmunology. Advances in Experimental Medicine and Biology, vol 602. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-72009-8_8

Download citation

Publish with us

Policies and ethics