Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1991 Sep 1;174(3):693–703. doi: 10.1084/jem.174.3.693

Differentiation of primitive human multipotent hematopoietic progenitors into single lineage clonogenic progenitors is accompanied by alterations in their interaction with fibronectin

PMCID: PMC2118931  PMID: 1875168

Abstract

We have previously demonstrated that primitive progenitors from human bone marrow termed long term bone marrow culture initiating cells (LTBMC-IC) adhere avidly to irradiated bone marrow stroma, while more mature clonogenic progenitors fail to do so. In this study we examine the interaction between these progenitors and components of the bone marrow stroma. (a) We demonstrate that both primitive LTBMC-IC and more mature clonogenic progenitors adhere to intact fibronectin. (b) Primitive LTBMC-IC and multi-lineage CFU-MIX progenitors adhere to the 33/66 kD COOH-terminal heparin-binding cell-adhesion promoting fragment of fibronectin, but adhere significantly less to its 75 kD RGDS- dependent cell-binding fragment. In contrast, more differentiated single-lineage progenitors adhere equally well to the 33/66 kD RGDS independent and the 75 kD RGDS-dependent cell-adhesion fragments of fibronectin. (c) Both primitive LTBMC-IC and clonogenic progenitors adhere to the three known cell-attachment sites in the 33/66 kD cell- adhesion promoting fragment, FN-C/H I, FN-C/H II and CS1. However, LTBMC-IC and CFU-MIX progenitors adhere significantly better to FN-C/H II than to the flanking FN-C/H I and CS1 cell-attachment sites. In contrast, single-lineage progenitors adhere equally well to all three cell attachment sites in the 33/66 kD cell-adhesion promoting fragment. (d) Finally, adhesion of primitive LTBMC-IC to intact irradiated stroma can be inhibited partially by peptide FN-C/H II and almost completely by a combination of FN-C/H II and peptide FN-C/H I and CS1. This study demonstrates that adhesive interactions between primitive hematopoietic progenitors and the extracellular matrix component fibronectin can occur. Specific changes in adhesion to the 33/66 kD cell-adhesion promoting fragment and the 75 kD RGDS-dependent cell-adhesion fragment of fibronectin are associated with differentiation of primitive multi- lineage progenitors into committed single-lineage progenitors. Such differences in adhesive interaction with fibronectin may allow hematopoietic progenitors at various stages of differentiation to interact with specific supportive loci of the bone marrow microenvironment. Finally, the ability to block adhesion of LTBMC-IC to intact irradiated stroma with peptides FN-C/H II, FN-C/H I and CS1 suggests that receptors responsible for this interaction may be important in the homing of primitive progenitors to the bone marrow.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aizawa S., Tavassoli M. In vitro homing of hemopoietic stem cells is mediated by a recognition system with galactosyl and mannosyl specificities. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4485–4489. doi: 10.1073/pnas.84.13.4485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andrews R. G., Singer J. W., Bernstein I. D. Human hematopoietic precursors in long-term culture: single CD34+ cells that lack detectable T cell, B cell, and myeloid cell antigens produce multiple colony-forming cells when cultured with marrow stromal cells. J Exp Med. 1990 Jul 1;172(1):355–358. doi: 10.1084/jem.172.1.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andrews R. G., Singer J. W., Bernstein I. D. Precursors of colony-forming cells in humans can be distinguished from colony-forming cells by expression of the CD33 and CD34 antigens and light scatter properties. J Exp Med. 1989 May 1;169(5):1721–1731. doi: 10.1084/jem.169.5.1721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barnett M. J., Eaves C. J., Phillips G. L., Kalousek D. K., Klingemann H. G., Lansdorp P. M., Reece D. E., Shepherd J. D., Shaw G. J., Eaves A. C. Successful autografting in chronic myeloid leukaemia after maintenance of marrow in culture. Bone Marrow Transplant. 1989 Jul;4(4):345–351. [PubMed] [Google Scholar]
  5. Bernardi P., Patel V. P., Lodish H. F. Lymphoid precursor cells adhere to two different sites on fibronectin. J Cell Biol. 1987 Jul;105(1):489–498. doi: 10.1083/jcb.105.1.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Campbell A. D., Long M. W., Wicha M. S. Haemonectin, a bone marrow adhesion protein specific for cells of granulocyte lineage. Nature. 1987 Oct 22;329(6141):744–746. doi: 10.1038/329744a0. [DOI] [PubMed] [Google Scholar]
  7. Campbell A., Wicha M. S., Long M. Extracellular matrix promotes the growth and differentiation of murine hematopoietic cells in vitro. J Clin Invest. 1985 Jun;75(6):2085–2090. doi: 10.1172/JCI111928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coulombel L., Vuillet M. H., Leroy C., Tchernia G. Lineage- and stage-specific adhesion of human hematopoietic progenitor cells to extracellular matrices from marrow fibroblasts. Blood. 1988 Feb;71(2):329–334. [PubMed] [Google Scholar]
  9. Del Rosso M., Cappelletti R., Dini G., Fibbi G., Vannucchi S., Chiarugi V., Guazzelli C. Involvement of glycosaminoglycans in detachment of early myeloid precursors from bone-marrow stromal cells. Biochim Biophys Acta. 1981 Aug 17;676(2):129–136. doi: 10.1016/0304-4165(81)90180-x. [DOI] [PubMed] [Google Scholar]
  10. Dexter T. M., Moore M. A., Sheridan A. P. Maintenance of hemopoietic stem cells and production of differentiated progeny in allogeneic and semiallogeneic bone marrow chimeras in vitro. J Exp Med. 1977 Jun 1;145(6):1612–1616. doi: 10.1084/jem.145.6.1612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fraser C. C., Eaves C. J., Szilvassy S. J., Humphries R. K. Expansion in vitro of retrovirally marked totipotent hematopoietic stem cells. Blood. 1990 Sep 15;76(6):1071–1076. [PubMed] [Google Scholar]
  12. Frassoni F., Testa N. G., Lord B. I. The relative spatial distribution of erythroid progenitor cells (BFUe and CFUe) in the normal mouse femur. Cell Tissue Kinet. 1982 Jul;15(4):447–455. doi: 10.1111/j.1365-2184.1982.tb01062.x. [DOI] [PubMed] [Google Scholar]
  13. Gordon M. Y., Riley G. P., Clarke D. Heparan sulfate is necessary for adhesive interactions between human early hemopoietic progenitor cells and the extracellular matrix of the marrow microenvironment. Leukemia. 1988 Dec;2(12):804–809. [PubMed] [Google Scholar]
  14. Guan J. L., Hynes R. O. Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor alpha 4 beta 1. Cell. 1990 Jan 12;60(1):53–61. doi: 10.1016/0092-8674(90)90715-q. [DOI] [PubMed] [Google Scholar]
  15. Haugen P. K., McCarthy J. B., Skubitz A. P., Furcht L. T., Letourneau P. C. Recognition of the A chain carboxy-terminal heparin binding region of fibronectin involves multiple sites: two contiguous sequences act independently to promote neural cell adhesion. J Cell Biol. 1990 Dec;111(6 Pt 1):2733–2745. doi: 10.1083/jcb.111.6.2733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Humphries M. J., Komoriya A., Akiyama S. K., Olden K., Yamada K. M. Identification of two distinct regions of the type III connecting segment of human plasma fibronectin that promote cell type-specific adhesion. J Biol Chem. 1987 May 15;262(14):6886–6892. [PubMed] [Google Scholar]
  17. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  18. Lemoine F. M., Dedhar S., Lima G. M., Eaves C. J. Transformation-associated alterations in interactions between pre-B cells and fibronectin. Blood. 1990 Dec 1;76(11):2311–2320. [PubMed] [Google Scholar]
  19. Long M. W., Dixit V. M. Thrombospondin functions as a cytoadhesion molecule for human hematopoietic progenitor cells. Blood. 1990 Jun 15;75(12):2311–2318. [PubMed] [Google Scholar]
  20. McCarthy J. B., Chelberg M. K., Mickelson D. J., Furcht L. T. Localization and chemical synthesis of fibronectin peptides with melanoma adhesion and heparin binding activities. Biochemistry. 1988 Feb 23;27(4):1380–1388. doi: 10.1021/bi00404a044. [DOI] [PubMed] [Google Scholar]
  21. McCarthy J. B., Hagen S. T., Furcht L. T. Human fibronectin contains distinct adhesion- and motility-promoting domains for metastatic melanoma cells. J Cell Biol. 1986 Jan;102(1):179–188. doi: 10.1083/jcb.102.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McCarthy J. B., Skubitz A. P., Qi Z., Yi X. Y., Mickelson D. J., Klein D. J., Furcht L. T. RGD-independent cell adhesion to the carboxy-terminal heparin-binding fragment of fibronectin involves heparin-dependent and -independent activities. J Cell Biol. 1990 Mar;110(3):777–787. doi: 10.1083/jcb.110.3.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Minguell J. J., Tavassoli M. Proteoglycan synthesis by hematopoietic progenitor cells. Blood. 1989 May 15;73(7):1821–1827. [PubMed] [Google Scholar]
  24. Morris A. J., Dexter T. M., Gallagher J. T. Metabolic properties of a homogeneous proteoglycan of a haemopoietic stem cell line, FDCP-mix. Biochem J. 1989 Jun 1;260(2):479–486. doi: 10.1042/bj2600479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Patel V. P., Lodish H. F. A fibronectin matrix is required for differentiation of murine erythroleukemia cells into reticulocytes. J Cell Biol. 1987 Dec;105(6 Pt 2):3105–3118. doi: 10.1083/jcb.105.6.3105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pearson H. A. Marrow hypoplasia in anorexia nervosa. J Pediatr. 1967 Aug;71(2):211–215. doi: 10.1016/s0022-3476(67)80074-x. [DOI] [PubMed] [Google Scholar]
  27. Peters C., O'Shea K. S., Campbell A. D., Wicha M. S., Long M. W. Fetal expression of hemonectin: an extracellular matrix hematopoietic cytoadhesion molecule. Blood. 1990 Jan 15;75(2):357–364. [PubMed] [Google Scholar]
  28. Pytela R., Pierschbacher M. D., Ruoslahti E. Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor. Cell. 1985 Jan;40(1):191–198. doi: 10.1016/0092-8674(85)90322-8. [DOI] [PubMed] [Google Scholar]
  29. Rosemblatt M., Vuillet-Gaugler M. H., Leroy C., Coulombel L. Coexpression of two fibronectin receptors, VLA-4 and VLA-5, by immature human erythroblastic precursor cells. J Clin Invest. 1991 Jan;87(1):6–11. doi: 10.1172/JCI115002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ruoslahti E. Fibronectin and its receptors. Annu Rev Biochem. 1988;57:375–413. doi: 10.1146/annurev.bi.57.070188.002111. [DOI] [PubMed] [Google Scholar]
  31. Ruoslahti E., Pierschbacher M. D. New perspectives in cell adhesion: RGD and integrins. Science. 1987 Oct 23;238(4826):491–497. doi: 10.1126/science.2821619. [DOI] [PubMed] [Google Scholar]
  32. Ryan D. H., Nuccie B. L., Abboud C. N., Liesveld J. L. Maturation-dependent adhesion of human B cell precursors to the bone marrow microenvironment. J Immunol. 1990 Jul 15;145(2):477–484. [PubMed] [Google Scholar]
  33. Savagner P., Imhof B. A., Yamada K. M., Thiery J. P. Homing of hemopoietic precursor cells to the embryonic thymus: characterization of an invasive mechanism induced by chemotactic peptides. J Cell Biol. 1986 Dec;103(6 Pt 2):2715–2727. doi: 10.1083/jcb.103.6.2715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Spooncer E., Gallagher J. T., Krizsa F., Dexter T. M. Regulation of haemopoiesis in long-term bone marrow cultures. IV. Glycosaminoglycan synthesis and the stimulation of haemopoiesis by beta-D-xylosides. J Cell Biol. 1983 Feb;96(2):510–514. doi: 10.1083/jcb.96.2.510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sutherland H. J., Eaves C. J., Eaves A. C., Dragowska W., Lansdorp P. M. Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro. Blood. 1989 Oct;74(5):1563–1570. [PubMed] [Google Scholar]
  36. Tavassoli M., Eastlund D. T., Yam L. T., Neiman R. S., Finkel H. Gelatinous transformation of bone marrow in prolonged self-induced starvation. Scand J Haematol. 1976 Apr;16(4):311–319. doi: 10.1111/j.1600-0609.1976.tb01156.x. [DOI] [PubMed] [Google Scholar]
  37. Tsai S., Patel V., Beaumont E., Lodish H. F., Nathan D. G., Sieff C. A. Differential binding of erythroid and myeloid progenitors to fibroblasts and fibronectin. Blood. 1987 Jun;69(6):1587–1594. [PubMed] [Google Scholar]
  38. Verfaillie C., Blakolmer K., McGlave P. Purified primitive human hematopoietic progenitor cells with long-term in vitro repopulating capacity adhere selectively to irradiated bone marrow stroma. J Exp Med. 1990 Aug 1;172(2):509–502. doi: 10.1084/jem.172.2.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Vuillet-Gaugler M. H., Breton-Gorius J., Vainchenker W., Guichard J., Leroy C., Tchernia G., Coulombel L. Loss of attachment to fibronectin with terminal human erythroid differentiation. Blood. 1990 Feb 15;75(4):865–873. [PubMed] [Google Scholar]
  40. Wayner E. A., Garcia-Pardo A., Humphries M. J., McDonald J. A., Carter W. G. Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin. J Cell Biol. 1989 Sep;109(3):1321–1330. doi: 10.1083/jcb.109.3.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Weinstein R., Riordan M. A., Wenc K., Kreczko S., Zhou M., Dainiak N. Dual role of fibronectin in hematopoietic differentiation. Blood. 1989 Jan;73(1):111–116. [PubMed] [Google Scholar]
  42. Weiss R. E., Reddi A. H. Appearance of fibronectin during the differentiation of cartilage, bone, and bone marrow. J Cell Biol. 1981 Mar;88(3):630–636. doi: 10.1083/jcb.88.3.630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Whitlock C. A., Witte O. N. Long-term culture of B lymphocytes and their precursors from murine bone marrow. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3608–3612. doi: 10.1073/pnas.79.11.3608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wight T. N., Kinsella M. G., Keating A., Singer J. W. Proteoglycans in human long-term bone marrow cultures: biochemical and ultrastructural analyses. Blood. 1986 May;67(5):1333–1343. [PubMed] [Google Scholar]
  45. Zuckerman K. S., Wicha M. S. Extracellular matrix production by the adherent cells of long-term murine bone marrow cultures. Blood. 1983 Mar;61(3):540–547. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES