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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Nov 1;89(21):10134–10138. doi: 10.1073/pnas.89.21.10134

The same exhaustible multilineage precursor produces both myeloid and lymphoid cells as early as 3-4 weeks after marrow transplantation.

D E Harrison 1, R K Zhong 1
PMCID: PMC50292  PMID: 1438202

Abstract

Hemopoietic precursors with the ability to differentiate into wide varieties of cell types are considered primitive, as are precursors with long-term repopulating ability. Here we study the populations of marrow precursors from which both myeloid and lymphoid lineages are descended shortly after transplantation. Surprisingly, few or none of these precursors show long-term repopulating ability. Equal portions of a mixture of marrow cells from C57BL/6J (B6) and congenic B6-Hbbd Gpi-1a mice are transplanted into a group of recipients. Three weeks later, highly significant correlations between percentages of B6 type T cells, B cells, granulocytes, and platelets in each recipient indicate that many lymphoid and myeloid cells are descended from common precursors. After 4-6 weeks, most correlations between lymphoid and myeloid cells improve, indicating that most or all differentiated cells are descended from common precursors. The more differentiated myeloid-specific precursors found in spleen colony-forming cell assays apparently fail to contribute significantly to the differentiated myeloid cell populations tested. By using the binomial model, in which variability of the data among the recipients is inversely related to the number of precursors in the mixture, donor precursor concentrations are estimated as approximately 21 per 10(5) marrow cells after 3 weeks, falling 3-fold to 6.6 per 10(5) after 4-6 weeks. This trend continues, with higher correlations, greater variabilities, and donor precursor concentrations of 1.9 per 10(5) marrow cells after 12-14 weeks and 1.4 per 10(5) after 24 weeks. Strong increases in variances between 3 and 12 weeks after transplantation suggest that most or all of the initially active multilineage precursors are exhausted during this time period. The fact that the ability of a hemopoietic stem cell to differentiate into widely disparate lineages is not associated with long-term repopulating ability requires a change in stem cell definitions, since primitive hemopoietic stem cells have traditionally been defined by both these abilities.

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Selected References

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  1. Capel B., Hawley R., Covarrubias L., Hawley T., Mintz B. Clonal contributions of small numbers of retrovirally marked hematopoietic stem cells engrafted in unirradiated neonatal W/Wv mice. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4564–4568. doi: 10.1073/pnas.86.12.4564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cumano A., Paige C. J., Iscove N. N., Brady G. Bipotential precursors of B cells and macrophages in murine fetal liver. Nature. 1992 Apr 16;356(6370):612–615. doi: 10.1038/356612a0. [DOI] [PubMed] [Google Scholar]
  3. Dick J. E., Magli M. C., Huszar D., Phillips R. A., Bernstein A. Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice. Cell. 1985 Aug;42(1):71–79. doi: 10.1016/s0092-8674(85)80102-1. [DOI] [PubMed] [Google Scholar]
  4. Harrison D. E., Astle C. M., Lerner C. Number and continuous proliferative pattern of transplanted primitive immunohematopoietic stem cells. Proc Natl Acad Sci U S A. 1988 Feb;85(3):822–826. doi: 10.1073/pnas.85.3.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Harrison D. E., Astle C. M., Stone M. Numbers and functions of transplantable primitive immunohematopoietic stem cells. Effects of age. J Immunol. 1989 Jun 1;142(11):3833–3840. [PubMed] [Google Scholar]
  6. Harrison D. E., Stone M., Astle C. M. Effects of transplantation on the primitive immunohematopoietic stem cell. J Exp Med. 1990 Aug 1;172(2):431–437. doi: 10.1084/jem.172.2.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hirayama F., Shih J. P., Awgulewitsch A., Warr G. W., Clark S. C., Ogawa M. Clonal proliferation of murine lymphohemopoietic progenitors in culture. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5907–5911. doi: 10.1073/pnas.89.13.5907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jordan C. T., Lemischka I. R. Clonal and systemic analysis of long-term hematopoiesis in the mouse. Genes Dev. 1990 Feb;4(2):220–232. doi: 10.1101/gad.4.2.220. [DOI] [PubMed] [Google Scholar]
  9. Jordan C. T., McKearn J. P., Lemischka I. R. Cellular and developmental properties of fetal hematopoietic stem cells. Cell. 1990 Jun 15;61(6):953–963. doi: 10.1016/0092-8674(90)90061-i. [DOI] [PubMed] [Google Scholar]
  10. Keller G., Snodgrass R. Life span of multipotential hematopoietic stem cells in vivo. J Exp Med. 1990 May 1;171(5):1407–1418. doi: 10.1084/jem.171.5.1407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Magli M. C., Iscove N. N., Odartchenko N. Transient nature of early haematopoietic spleen colonies. Nature. 1982 Feb 11;295(5849):527–529. doi: 10.1038/295527a0. [DOI] [PubMed] [Google Scholar]
  12. Micklem H. S., Lennon J. E., Ansell J. D., Gray R. A. Numbers and dispersion of repopulating hematopoietic cell clones in radiation chimeras as functions of injected cell dose. Exp Hematol. 1987 Mar;15(3):251–257. [PubMed] [Google Scholar]
  13. Smith L. G., Weissman I. L., Heimfeld S. Clonal analysis of hematopoietic stem-cell differentiation in vivo. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2788–2792. doi: 10.1073/pnas.88.7.2788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Spangrude G. J., Heimfeld S., Weissman I. L. Purification and characterization of mouse hematopoietic stem cells. Science. 1988 Jul 1;241(4861):58–62. doi: 10.1126/science.2898810. [DOI] [PubMed] [Google Scholar]
  15. Stone M., Harrison D. A stratified binomial marker model for bone-marrow repopulation experiments. J Theor Biol. 1990 May 22;144(2):267–273. doi: 10.1016/s0022-5193(05)80325-x. [DOI] [PubMed] [Google Scholar]
  16. Stone M. Variance-covariance modeling with chromosome markers. J Theor Biol. 1984 Mar 21;107(2):275–286. doi: 10.1016/s0022-5193(84)80028-4. [DOI] [PubMed] [Google Scholar]
  17. Szilvassy S. J., Fraser C. C., Eaves C. J., Lansdorp P. M., Eaves A. C., Humphries R. K. Retrovirus-mediated gene transfer to purified hemopoietic stem cells with long-term lympho-myelopoietic repopulating ability. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8798–8802. doi: 10.1073/pnas.86.22.8798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Van Zant G., Eldridge P. W., Behringer R. R., Dewey M. J. Genetic control of hematopoietic kinetics revealed by analyses of allophenic mice and stem cell suicide. Cell. 1983 Dec;35(3 Pt 2):639–645. doi: 10.1016/0092-8674(83)90096-x. [DOI] [PubMed] [Google Scholar]
  20. Wu A. M., Till J. E., Siminovitch L., McCulloch E. A. A cytological study of the capacity for differentiation of normal hemopoietic colony-forming cells. J Cell Physiol. 1967 Apr;69(2):177–184. doi: 10.1002/jcp.1040690208. [DOI] [PubMed] [Google Scholar]

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