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. 1996 Dec 16;15(24):6869–6876.

Primitive lymphohematopoietic precursor cell lines generated in culture from day 7 early-mid-primitive streak stage mouse embryo.

R Palacios 1, B A Imhof 1
PMCID: PMC452513  PMID: 9003763

Abstract

During mouse development, the first lymphohematopoietic precursor cells and myeloid or erythroid cell lineage-determined cells can be detected in the yolk sac at days 8-8.5 of gestation. The characteristics of the cells that give rise to these yolk sac primitive lymphohematopoietic cells and the molecular events controlling this process remain poorly defined. We show here that cell suspensions from day 7 early-mid-primitive streak stage embryo proper generated early immature PgP-1+ Joro 177+ Lin- hematopoietic cells and some Mac-1+ myeloid and TER 119+ erythroid cells after co-culture with the yolk sac-derived stromal cell line YS6 without addition of exogenous cytokines. Purified Lin- hematopoietic cells generated in these cultures did not express genes known to be transcribed at early stages of lymphoid, myeloid or erythroid cell differentiation and were able to give rise to T and B lymphocytes, myeloid cells and erythroid cells after appropriate further induction in vitro. Several cell lines were established in culture with a mixture of four cytokines from the PgP-1+ Joro 177+ Lin- cell population. The cell lines shared phenotypic and genotypic characteristics with the PgP-1+ Joro 177+ Lin- cell population generated in culture from day 7 embryo proper and they were able to reconstitute the lymphohematopoietic system of irradiated mice. Taken together these results support a model of lymphohematopoiesis in which cells from day 7 early-mid-primitive streak mouse embryo proper migrate and colonize the visceral yolk sac. There they generate primitive lymphohematopoietic precursor cells and the first erythroid and myeloid hematopoietic cells under the influence of yolk sac stromal cells like the YS6 cells described here.

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Selected References

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

  1. Bain G., Maandag E. C., Izon D. J., Amsen D., Kruisbeek A. M., Weintraub B. C., Krop I., Schlissel M. S., Feeney A. J., van Roon M. E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements. Cell. 1994 Dec 2;79(5):885–892. doi: 10.1016/0092-8674(94)90077-9. [DOI] [PubMed] [Google Scholar]
  2. Fennie C., Cheng J., Dowbenko D., Young P., Lasky L. A. CD34+ endothelial cell lines derived from murine yolk sac induce the proliferation and differentiation of yolk sac CD34+ hematopoietic progenitors. Blood. 1995 Dec 15;86(12):4454–4467. [PubMed] [Google Scholar]
  3. Godin I., Dieterlen-Lièvre F., Cumano A. B-lymphoid potential in pre-liver mouse embryo. Semin Immunol. 1995 Jun;7(3):131–141. doi: 10.1016/1044-5323(95)90041-1. [DOI] [PubMed] [Google Scholar]
  4. Gross J. A., Appleby M. W., Chien S., Nada S., Bartelmez S. H., Okada M., Aizawa S., Perlmutter R. M. Control of lymphopoiesis by p50csk, a regulatory protein tyrosine kinase. J Exp Med. 1995 Feb 1;181(2):463–473. doi: 10.1084/jem.181.2.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Huang H., Auerbach R. Identification and characterization of hematopoietic stem cells from the yolk sac of the early mouse embryo. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10110–10114. doi: 10.1073/pnas.90.21.10110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ikuta K., Kina T., MacNeil I., Uchida N., Peault B., Chien Y. H., Weissman I. L. A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells. Cell. 1990 Sep 7;62(5):863–874. doi: 10.1016/0092-8674(90)90262-d. [DOI] [PubMed] [Google Scholar]
  7. Ikuta K., Uchida N., Friedman J., Weissman I. L. Lymphocyte development from stem cells. Annu Rev Immunol. 1992;10:759–783. doi: 10.1146/annurev.iy.10.040192.003551. [DOI] [PubMed] [Google Scholar]
  8. Keller G., Kennedy M., Papayannopoulou T., Wiles M. V. Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol. 1993 Jan;13(1):473–486. doi: 10.1128/mcb.13.1.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kincade P. W. Formation of B lymphocytes in fetal and adult life. Adv Immunol. 1981;31:177–245. doi: 10.1016/s0065-2776(08)60921-9. [DOI] [PubMed] [Google Scholar]
  10. Kincade P. W., Lee G., Watanabe T., Sun L., Scheid M. P. Antigens displayed on murine B lymphocyte precursors. J Immunol. 1981 Dec;127(6):2262–2268. [PubMed] [Google Scholar]
  11. Leiden J. M. Transcriptional regulation of T cell receptor genes. Annu Rev Immunol. 1993;11:539–570. doi: 10.1146/annurev.iy.11.040193.002543. [DOI] [PubMed] [Google Scholar]
  12. Medvinsky A. L., Samoylina N. L., Müller A. M., Dzierzak E. A. An early pre-liver intraembryonic source of CFU-S in the developing mouse. Nature. 1993 Jul 1;364(6432):64–67. doi: 10.1038/364064a0. [DOI] [PubMed] [Google Scholar]
  13. Melchers F., Karasuyama H., Haasner D., Bauer S., Kudo A., Sakaguchi N., Jameson B., Rolink A. The surrogate light chain in B-cell development. Immunol Today. 1993 Feb;14(2):60–68. doi: 10.1016/0167-5699(93)90060-X. [DOI] [PubMed] [Google Scholar]
  14. Moore M. A., Metcalf D. Ontogeny of the haemopoietic system: yolk sac origin of in vivo and in vitro colony forming cells in the developing mouse embryo. Br J Haematol. 1970 Mar;18(3):279–296. doi: 10.1111/j.1365-2141.1970.tb01443.x. [DOI] [PubMed] [Google Scholar]
  15. Moore M. A., Owen J. J. Experimental studies on the development of the thymus. J Exp Med. 1967 Oct 1;126(4):715–726. doi: 10.1084/jem.126.4.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Motoyama N., Wang F., Roth K. A., Sawa H., Nakayama K., Nakayama K., Negishi I., Senju S., Zhang Q., Fujii S. Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science. 1995 Mar 10;267(5203):1506–1510. doi: 10.1126/science.7878471. [DOI] [PubMed] [Google Scholar]
  17. Müller A. M., Medvinsky A., Strouboulis J., Grosveld F., Dzierzak E. Development of hematopoietic stem cell activity in the mouse embryo. Immunity. 1994 Jul;1(4):291–301. doi: 10.1016/1074-7613(94)90081-7. [DOI] [PubMed] [Google Scholar]
  18. Orkin S. H. Transcription factors and hematopoietic development. J Biol Chem. 1995 Mar 10;270(10):4955–4958. doi: 10.1074/jbc.270.10.4955. [DOI] [PubMed] [Google Scholar]
  19. Palacios R., Bucana C., Xie X. Long-term culture of lymphohematopoietic stem cells. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5247–5252. doi: 10.1073/pnas.93.11.5247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Palacios R., Golunski E., Samaridis J. In vitro generation of hematopoietic stem cells from an embryonic stem cell line. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7530–7534. doi: 10.1073/pnas.92.16.7530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Palacios R., Imhof B. A. At day 8-8.5 of mouse development the yolk sac, not the embryo proper, has lymphoid precursor potential in vivo and in vitro. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6581–6585. doi: 10.1073/pnas.90.14.6581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Palacios R., Samaridis J. Bone marrow clones representing an intermediate stage of development between hematopoietic stem cells and pro-T-lymphocyte or pro-B-lymphocyte progenitors. Blood. 1993 Mar 1;81(5):1222–1238. [PubMed] [Google Scholar]
  23. Palacios R., Samaridis J., Thorpe D., Leu T. Identification and characterization of pro-T lymphocytes and lineage-uncommitted lymphocyte precursors from mice with three novel surface markers. J Exp Med. 1990 Jul 1;172(1):219–230. doi: 10.1084/jem.172.1.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Palacios R., Samaridis J. Thymus colonization in the developing mouse embryo. Eur J Immunol. 1991 Jan;21(1):109–113. doi: 10.1002/eji.1830210117. [DOI] [PubMed] [Google Scholar]
  25. Palacios R., Stuber S., Rolink A. The epigenetic influences of bone marrow and fetal liver stroma cells on the developmental potential of Ly-1+ pro-B lymphocyte clones. Eur J Immunol. 1989 Feb;19(2):347–356. doi: 10.1002/eji.1830190220. [DOI] [PubMed] [Google Scholar]
  26. Shivdasani R. A., Mayer E. L., Orkin S. H. Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL. Nature. 1995 Feb 2;373(6513):432–434. doi: 10.1038/373432a0. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Spanopoulou E., Roman C. A., Corcoran L. M., Schlissel M. S., Silver D. P., Nemazee D., Nussenzweig M. C., Shinton S. A., Hardy R. R., Baltimore D. Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice. Genes Dev. 1994 May 1;8(9):1030–1042. doi: 10.1101/gad.8.9.1030. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Trowbridge I. S., Lesley J., Schulte R., Hyman R., Trotter J. Biochemical characterization and cellular distribution of a polymorphic, murine cell-surface glycoprotein expressed on lymphoid tissues. Immunogenetics. 1982 Mar;15(3):299–312. doi: 10.1007/BF00364338. [DOI] [PubMed] [Google Scholar]
  31. Warren A. P., Patel K., McConkey D. J., Palacios R. CD98: a type II transmembrane glycoprotein expressed from the beginning of primitive and definitive hematopoiesis may play a critical role in the development of hematopoietic cells. Blood. 1996 May 1;87(9):3676–3687. [PubMed] [Google Scholar]
  32. Yoder M. C., Papaioannou V. E., Breitfeld P. P., Williams D. A. Murine yolk sac endoderm- and mesoderm-derived cell lines support in vitro growth and differentiation of hematopoietic cells. Blood. 1994 May 1;83(9):2436–2443. [PubMed] [Google Scholar]
  33. Young F., Ardman B., Shinkai Y., Lansford R., Blackwell T. K., Mendelsohn M., Rolink A., Melchers F., Alt F. W. Influence of immunoglobulin heavy- and light-chain expression on B-cell differentiation. Genes Dev. 1994 May 1;8(9):1043–1057. doi: 10.1101/gad.8.9.1043. [DOI] [PubMed] [Google Scholar]

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