Abstract
Three distinct hematopoietic populations derived from normal bone marrow were analyzed for their response to defined growth factors. The Thy-1loT- B- G- M-population, composing 0.2% of bone marrow, is 370- fold enriched for pluripotent hematopoietic stem cells. The two other populations, the Thy-1- T- B- G- M- and the predominantly mature Thy-1+ T+ B+ G+ M+ cells, lack stem cells. Thy-1loT- B- G- M- cells respond with a frequency of one in seven cells to IL-3 in an in vitro CFU-C assay, and give rise to many mixed colonies as expected from an early multipotent or pluripotent progenitor. The Thy-1- T- B- G- M- population also contains progenitor cells which responded to IL-3. However, colonies derived from Thy-1- T- B- G- M- cells are almost exclusively restricted to the macrophage/granulocyte lineages. This indicates that IL-3 can stimulate at least two distinct clonogenic early progenitor cells in normal bone marrow: multipotent Thy-1loT- B- G- M- cells and restricted Thy-1- T- B- G- M- cells. Thy-1loT- B- G- M- cells could not be stimulated by macrophage colony-stimulating factor (M-CSF), granulocyte CSF (G-CSF) or IL-5 (Eosinophil-CSF). The hematopoietic precursors that react to these factors are enriched in the Thy-1- T- G- B- M- population. Thus, multipotent and restricted progenitors can be separated on the basis of the expression of the cell surface antigen Thy-1.
Full Text
The Full Text of this article is available as a PDF (1.1 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Basch R. S., Berman J. W. Thy-1 determinants are present on many murine hematopoietic cells other than T cells. Eur J Immunol. 1982 May;12(5):359–364. doi: 10.1002/eji.1830120502. [DOI] [PubMed] [Google Scholar]
- Berman J. W., Basch R. S. Thy-1 antigen expression by murine hematopoietic precursor cells. Exp Hematol. 1985 Dec;13(11):1152–1156. [PubMed] [Google Scholar]
- Bertoncello I., Bartelmez S. H., Bradley T. R., Stanley E. R., Harris R. A., Sandrin M. S., Kriegler A. B., McNiece I. K., Hunter S. D., Hodgson G. S. Isolation and analysis of primitive hemopoietic progenitor cells on the basis of differential expression of Qa-m7 antigen. J Immunol. 1986 May 1;136(9):3219–3224. [PubMed] [Google Scholar]
- Boswell H. S., Wade P. M., Jr, Quesenberry P. J. Thy-1 antigen expression by murine high-proliferative capacity hematopoietic progenitor cells. I. Relation between sensitivity to depletion by Thy-1 antibody and stem cell generation potential. J Immunol. 1984 Dec;133(6):2940–2949. [PubMed] [Google Scholar]
- Burgess A. W., Metcalf D. The nature and action of granulocyte-macrophage colony stimulating factors. Blood. 1980 Dec;56(6):947–958. [PubMed] [Google Scholar]
- Clark S. C., Kamen R. The human hematopoietic colony-stimulating factors. Science. 1987 Jun 5;236(4806):1229–1237. doi: 10.1126/science.3296190. [DOI] [PubMed] [Google Scholar]
- Coffman R. L. Surface antigen expression and immunoglobulin gene rearrangement during mouse pre-B cell development. Immunol Rev. 1982;69:5–23. doi: 10.1111/j.1600-065x.1983.tb00446.x. [DOI] [PubMed] [Google Scholar]
- Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
- Goldschneider I., Gordon L. K., Morris R. J. Demonstration of Thy-1 antigen on pluripotent hemopoietic stem cells in the rat. J Exp Med. 1978 Nov 1;148(5):1351–1366. doi: 10.1084/jem.148.5.1351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harada N., Kikuchi Y., Tominaga A., Takaki S., Takatsu K. BCGFII activity on activated B cells of a purified murine T cell-replacing factor (TRF) from a T cell hybridoma (B151K12). J Immunol. 1985 Jun;134(6):3944–3951. [PubMed] [Google Scholar]
- Hodgson G. S., Bradley T. R. Properties of haematopoietic stem cells surviving 5-fluorouracil treatment: evidence for a pre-CFU-S cell? Nature. 1979 Oct 4;281(5730):381–382. doi: 10.1038/281381a0. [DOI] [PubMed] [Google Scholar]
- Holmes K. L., Langdon W. Y., Fredrickson T. N., Coffman R. L., Hoffman P. M., Hartley J. W., Morse H. C., 3rd Analysis of neoplasms induced by Cas-Br-M MuLV tumor extracts. J Immunol. 1986 Jul 15;137(2):679–688. [PubMed] [Google Scholar]
- Hunt S. V. The presence of Thy-1 on the surface of rat lymphoid stem cells and colony-forming units. Eur J Immunol. 1979 Nov;9(11):853–859. doi: 10.1002/eji.1830091105. [DOI] [PubMed] [Google Scholar]
- Ihle J. N., Keller J., Oroszlan S., Henderson L. E., Copeland T. D., Fitch F., Prystowsky M. B., Goldwasser E., Schrader J. W., Palaszynski E. Biologic properties of homogeneous interleukin 3. I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, p cell-stimulating factor activity, colony-stimulating factor activity, and histamine-producing cell-stimulating factor activity. J Immunol. 1983 Jul;131(1):282–287. [PubMed] [Google Scholar]
- Iscove N. N., Sieber F. Erythroid progenitors in mouse bone marrow detected by macroscopic colony formation in culture. Exp Hematol. 1975 Jan;3(1):32–43. [PubMed] [Google Scholar]
- Koike K., Stanley E. R., Ihle J. N., Ogawa M. Macrophage colony formation supported by purified CSF-1 and/or interleukin 3 in serum-free culture: evidence for hierarchical difference in macrophage colony-forming cells. Blood. 1986 Apr;67(4):859–864. [PubMed] [Google Scholar]
- Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
- McCarthy K. F., Hale M. L., Fehnel P. L. Purification and analysis of rat hematopoietic stem cells by flow cytometry. Cytometry. 1987 May;8(3):296–305. doi: 10.1002/cyto.990080310. [DOI] [PubMed] [Google Scholar]
- McGrath M. S., Pillemer E., Weissman I. L. Murine leukaemogenesis: monoclonal antibodies to T-cell determinants arrest T-lymphoma cell proliferation. Nature. 1980 May 22;285(5762):259–261. doi: 10.1038/285259a0. [DOI] [PubMed] [Google Scholar]
- Metcalf D., Johnson G. R., Burgess A. W. Direct stimulation by purified GM-CSF of the proliferation of multipotential and erythroid precursor cells. Blood. 1980 Jan;55(1):138–147. [PubMed] [Google Scholar]
- Miller B. A., Antognetti G., Springer T. A. Identification of cell surface antigens present on murine hematopoietic stem cells. J Immunol. 1985 May;134(5):3286–3290. [PubMed] [Google Scholar]
- Miller B. A., Lipton J. M., Linch D. C., Burakoff S. J., Nathan D. G. Thy-1 is a differentiation antigen that characterizes immature murine erythroid and myeloid hematopoietic progenitors. J Cell Physiol. 1985 Apr;123(1):25–32. doi: 10.1002/jcp.1041230105. [DOI] [PubMed] [Google Scholar]
- Miyatake S., Otsuka T., Yokota T., Lee F., Arai K. Structure of the chromosomal gene for granulocyte-macrophage colony stimulating factor: comparison of the mouse and human genes. EMBO J. 1985 Oct;4(10):2561–2568. doi: 10.1002/j.1460-2075.1985.tb03971.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muller-Sieburg C. E., Whitlock C. A., Weissman I. L. Isolation of two early B lymphocyte progenitors from mouse marrow: a committed pre-pre-B cell and a clonogenic Thy-1-lo hematopoietic stem cell. Cell. 1986 Feb 28;44(4):653–662. doi: 10.1016/0092-8674(86)90274-6. [DOI] [PubMed] [Google Scholar]
- Ogawa M., Porter P. N., Nakahata T. Renewal and commitment to differentiation of hemopoietic stem cells (an interpretive review). Blood. 1983 May;61(5):823–829. [PubMed] [Google Scholar]
- Prystowsky M. B., Otten G., Naujokas M. F., Vardiman J., Ihle J. N., Goldwasser E., Fitch F. W. Multiple hemopoietic lineages are found after stimulation of mouse bone marrow precursor cells with interleukin 3. Am J Pathol. 1984 Nov;117(2):171–179. [PMC free article] [PubMed] [Google Scholar]
- Quesenberry P., Song Z. X., McGrath E., McNiece I., Shadduck R., Waheed A., Baber G., Kleeman E., Kaiser D. Multilineage synergistic activity produced by a murine adherent marrow cell line. Blood. 1987 Mar;69(3):827–835. [PubMed] [Google Scholar]
- Rennick D. M., Lee F. D., Yokota T., Arai K. I., Cantor H., Nabel G. J. A cloned MCGF cDNA encodes a multilineage hematopoietic growth factor: multiple activities of interleukin 3. J Immunol. 1985 Feb;134(2):910–914. [PubMed] [Google Scholar]
- Rennick D., Yang G., Muller-Sieburg C., Smith C., Arai N., Takabe Y., Gemmell L. Interleukin 4 (B-cell stimulatory factor 1) can enhance or antagonize the factor-dependent growth of hemopoietic progenitor cells. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6889–6893. doi: 10.1073/pnas.84.19.6889. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosendaal M., Hodgson G. S., Bradley T. R. Organization of haemopoietic stem cells: the generation-age hypothesis. Cell Tissue Kinet. 1979 Jan;12(1):17–29. doi: 10.1111/j.1365-2184.1979.tb00110.x. [DOI] [PubMed] [Google Scholar]
- Sachs L. The molecular control of blood cell development. Science. 1987 Dec 4;238(4832):1374–1379. doi: 10.1126/science.3317831. [DOI] [PubMed] [Google Scholar]
- Sanderson C. J., O'Garra A., Warren D. J., Klaus G. G. Eosinophil differentiation factor also has B-cell growth factor activity: proposed name interleukin 4. Proc Natl Acad Sci U S A. 1986 Jan;83(2):437–440. doi: 10.1073/pnas.83.2.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sieff C. A., Emerson S. G., Donahue R. E., Nathan D. G., Wang E. A., Wong G. G., Clark S. C. Human recombinant granulocyte-macrophage colony-stimulating factor: a multilineage hematopoietin. Science. 1985 Dec 6;230(4730):1171–1173. doi: 10.1126/science.3877981. [DOI] [PubMed] [Google Scholar]
- Spangrude G. J., Muller-Sieburg C. E., Heimfeld S., Weissman I. L. Two rare populations of mouse Thy-1lo bone marrow cells repopulate the thymus. J Exp Med. 1988 May 1;167(5):1671–1683. doi: 10.1084/jem.167.5.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Springer T., Galfré G., Secher D. S., Milstein C. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol. 1979 Apr;9(4):301–306. doi: 10.1002/eji.1830090410. [DOI] [PubMed] [Google Scholar]
- Stanley E. R., Bartocci A., Patinkin D., Rosendaal M., Bradley T. R. Regulation of very primitive, multipotent, hemopoietic cells by hemopoietin-1. Cell. 1986 Jun 6;45(5):667–674. doi: 10.1016/0092-8674(86)90781-6. [DOI] [PubMed] [Google Scholar]
- Stanley E. R., Heard P. M. Factors regulating macrophage production and growth. Purification and some properties of the colony stimulating factor from medium conditioned by mouse L cells. J Biol Chem. 1977 Jun 25;252(12):4305–4312. [PubMed] [Google Scholar]
- Suda T., Suda J., Ogawa M. Disparate differentiation in mouse hemopoietic colonies derived from paired progenitors. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2520–2524. doi: 10.1073/pnas.81.8.2520. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Suda T., Suda J., Ogawa M., Ihle J. N. Permissive role of interleukin 3 (IL-3) in proliferation and differentiation of multipotential hemopoietic progenitors in culture. J Cell Physiol. 1985 Aug;124(2):182–190. doi: 10.1002/jcp.1041240203. [DOI] [PubMed] [Google Scholar]
- Swain S. L., Dutton R. W. Production of a B cell growth-promoting activity, (DL)BCGF, from a cloned T cell line and its assay on the BCL1 B cell tumor. J Exp Med. 1982 Dec 1;156(6):1821–1834. doi: 10.1084/jem.156.6.1821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- TILL J. E., McCULLOCH E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961 Feb;14:213–222. [PubMed] [Google Scholar]
- Van Zant G. Studies of hematopoietic stem cells spared by 5-fluorouracil. J Exp Med. 1984 Mar 1;159(3):679–690. doi: 10.1084/jem.159.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Visser J. W., Bauman J. G., Mulder A. H., Eliason J. F., de Leeuw A. M. Isolation of murine pluripotent hemopoietic stem cells. J Exp Med. 1984 Jun 1;159(6):1576–1590. doi: 10.1084/jem.159.6.1576. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker F., Nicola N. A., Metcalf D., Burgess A. W. Hierarchical down-modulation of hemopoietic growth factor receptors. Cell. 1985 Nov;43(1):269–276. doi: 10.1016/0092-8674(85)90032-7. [DOI] [PubMed] [Google Scholar]
- Williams D. E., Boswell H. S., Floyd A. D., Broxmeyer H. E. Pluripotential hematopoietic stem cells in post-5-fluorouracil murine bone marrow express the Thy-1 antigen. J Immunol. 1985 Aug;135(2):1004–1011. [PubMed] [Google Scholar]
- Yokota T., Coffman R. L., Hagiwara H., Rennick D. M., Takebe Y., Yokota K., Gemmell L., Shrader B., Yang G., Meyerson P. Isolation and characterization of lymphokine cDNA clones encoding mouse and human IgA-enhancing factor and eosinophil colony-stimulating factor activities: relationship to interleukin 5. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7388–7392. doi: 10.1073/pnas.84.21.7388. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yokota T., Lee F., Rennick D., Hall C., Arai N., Mosmann T., Nabel G., Cantor H., Arai K. Isolation and characterization of a mouse cDNA clone that expresses mast-cell growth-factor activity in monkey cells. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1070–1074. doi: 10.1073/pnas.81.4.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]