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. 1984 Mar 1;159(3):731–745. doi: 10.1084/jem.159.3.731

Development of adult bone marrow stem cells in H-2-compatible and - incompatible mouse fetuses

PMCID: PMC2187243  PMID: 6607968

Abstract

Bone marrow of normal adult mice was found, after transplacental inoculation, to contain cells still able to seed the livers of early fetuses. The recipients' own hematopoietic stem cells, with a W-mutant defect, were at a selective disadvantage. Progression of donor strain cells to the bone marrow, long-term self-renewal, and differentiation into myeloid and lymphoid derivatives was consistent with the engraftment of totipotent hematopoietic stem cells (THSC) comparable to precursors previously identified (4) in normal fetal liver. More limited stem cells, specific for the myeloid or lymphoid cell lineages, were not detected in adult bone marrow. The bone marrow THSC, however, had a generally lower capacity for self-renewal than did fetal liver THSC. They had also embarked upon irreversible changes in gene expression, including partial histocompatibility restriction. While completely allogeneic fetal liver THSC were readily accepted by fetuses, H-2 incompatibility only occasionally resulted in engraftment of adult bone marrow cells and, in these cases, was often associated with sudden death at 3-5 mo. On the other hand, H-2 compatibility, even with histocompatibility differences at other loci, was sufficient to ensure long-term success as often as with fetal liver THSC.

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Selected References

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  1. Abramson S., Miller R. G., Phillips R. A. The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid systems. J Exp Med. 1977 Jun 1;145(6):1567–1579. doi: 10.1084/jem.145.6.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aizawa S., Sado T., Kamisaku H., Kubo E. Cellular basis of the immunohematologic defects observed in short-term semiallogeneic B6C3F1 -- C3H chimeras: evidence for host-versus-graft reaction initiated by radioresistant T cells. Cell Immunol. 1980 Nov;56(1):47–57. doi: 10.1016/0008-8749(80)90080-5. [DOI] [PubMed] [Google Scholar]
  3. BILLINGHAM R. E., BRENT L., MEDAWAR P. B. Actively acquired tolerance of foreign cells. Nature. 1953 Oct 3;172(4379):603–606. doi: 10.1038/172603a0. [DOI] [PubMed] [Google Scholar]
  4. BORGHESE E. The present state of research on WW mice. Acta Anat (Basel) 1959;36(3):185–220. doi: 10.1159/000141435. [DOI] [PubMed] [Google Scholar]
  5. Clark E. A., Harmon R. C. Genetic control of natural cytotoxicity and hybrid resistance. Adv Cancer Res. 1980;31:227–285. doi: 10.1016/s0065-230x(08)60659-4. [DOI] [PubMed] [Google Scholar]
  6. Cudkowicz G., Bennett M. Peculiar immunobiology of bone marrow allografts. I. Graft rejection by irradiated responder mice. J Exp Med. 1971 Jul 1;134(1):83–102. doi: 10.1084/jem.134.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cudkowicz G., Bennett M. Peculiar immunobiology of bone marrow allografts. II. Rejection of parental grafts by resistant F 1 hybrid mice. J Exp Med. 1971 Dec 1;134(6):1513–1528. doi: 10.1084/jem.134.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fleischman R. A., Custer R. P., Mintz B. Totipotent hematopoietic stem cells: normal self-renewal and differentiation after transplantation between mouse fetuses. Cell. 1982 Sep;30(2):351–359. doi: 10.1016/0092-8674(82)90233-1. [DOI] [PubMed] [Google Scholar]
  9. Fleischman R. A., Mintz B. Prevention of genetic anemias in mice by microinjection of normal hematopoietic stem cells into the fetal placenta. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5736–5740. doi: 10.1073/pnas.76.11.5736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Greenberger J. S., Donahue D., Sakakeeny M. Induction of ecotropic endogenous murine leukemia virus in long-term bone marrow cultures from mouse strains of varying natural leukemia incidence. J Reticuloendothel Soc. 1979 Dec;26(6):839–853. [PubMed] [Google Scholar]
  11. Harrison D. E. Use of genetic anaemias in mice as tools for haematological research. Clin Haematol. 1979 Jun;8(2):239–262. [PubMed] [Google Scholar]
  12. Heidt P. J., Wagemaker G., Knaan-Shanzer S., van Bekkum D. W. Two distinct types of late onset graft-versus-host disease after bone marrow transplantation in lethally irradiated mice. Transplantation. 1981 Sep;32(3):263–264. [PubMed] [Google Scholar]
  13. Klein J. List of congenic lines of mice. I. Lines with differences at alloantigen loci. Transplantation. 1973 Jan;15(1):137–153. doi: 10.1097/00007890-197301000-00021. [DOI] [PubMed] [Google Scholar]
  14. Lipton J. M., Nathan D. G. Cell-cell interactions in the regulation of erythropoiesis. Br J Haematol. 1983 Mar;53(3):361–367. doi: 10.1111/j.1365-2141.1983.tb02036.x. [DOI] [PubMed] [Google Scholar]
  15. MCCULLOCH E. A., SIMINOVITCH L., TILL J. E. SPLEEN-COLONY FORMATION IN ANEMIC MICE OF GENOTYPE WW. Science. 1964 May 15;144(3620):844–846. doi: 10.1126/science.144.3620.844. [DOI] [PubMed] [Google Scholar]
  16. Micklem H. S., Ford C. E., Evans E. P., Ogden D. A., Papworth D. S. Competitive in vivo proliferation of foetal and adult haematopoietic cells in lethally irradiated mice. J Cell Physiol. 1972 Apr;79(2):293–298. doi: 10.1002/jcp.1040790214. [DOI] [PubMed] [Google Scholar]
  17. RUSSELL E. S., FONDAL E. L. Quantitative analysis of the normal and four alternative degrees of an inherited macrocytic anemia in the house mouse. I. Number and size of erythrocytes. Blood. 1951 Oct;6(10):892–905. [PubMed] [Google Scholar]
  18. Reimann J., Burger H. In vitro proliferation of haemopoietic cells in the presence of adherent cell layers. I. Culture conditions and strain dependence. Exp Hematol. 1979 Jan;7(1):45–51. [PubMed] [Google Scholar]
  19. Singer A., Hodes R. J. Mechanisms of T cell-B cell interaction. Annu Rev Immunol. 1983;1:211–241. doi: 10.1146/annurev.iy.01.040183.001235. [DOI] [PubMed] [Google Scholar]
  20. Whitney J. B., 3rd Simplified typing of mouse hemoglobin (Hbb) phenotypes using cystamine. Biochem Genet. 1978 Aug;16(7-8):667–672. doi: 10.1007/BF00484723. [DOI] [PubMed] [Google Scholar]
  21. Zinkernagel R. M., Althage A., Callahan G., Welsh R. M., Jr On the immunocompetence of H-2 incompatible irradiation bone marrow chimeras. J Immunol. 1980 May;124(5):2356–2365. [PubMed] [Google Scholar]

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