Abstract
The primary sites of hematopoiesis change during murine ontogeny. The first blood cells emerge in two waves in the yolk sac; primitive erythroblasts, megakaryocytes, and macrophages emerge on embryonic d (E) 7.0, whereas definitive progenitor cells appear as clusters within the yolk sac vasculature on E8.25. Of interest, yolk sac cells isolated prior to d 10.5 fail to engraft in myeloablated adult recipient mice and do not reconstitute hematopoiesis. We describe a method of sublethally myeloablating newborn mice in which E9.0 yolk sac cells engraft and repopulate all lineages of the hematopoietic system for up to 12 mo in primary recipients and up to 6 mo in secondary recipients. The exact mechanisms that permit yolk sac engraftment in the conditioned newborn mice remain elusive, but this method has been used by a number of investigators to pursue transplantation studies using embryo- or fetal-derived donor cells.
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References
Palis, J. and Yoder, M. (2001) Yolk sac hematopoiesis-the first blood cells of mouse and man. Exp. Hematol. 29, 927–936.
Palis, J., Robertson, S., Kennedy, M., Wall, C., and Keller, G. (1999) Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development 126, 5073–5081.
Xu, M.-J., Matsuoka, S., Yang, F.-C., Ebihara, Y., Manabe, A., Tanaka, R., et al. (2001) Evidence for the presence of murine primitive megakaryocytopoiesis in the early yolk sac. Blood 97, 2016–2022.
Palis, J., Chan, R., Koniski, A., Patel, R., Starr, M., and Yoder, M. (2001) Spatial and temporal emergence of high proliferative potential hematopoietic precursors during murine embryogenesis. Proc. Natl. Acad. Sci. USA 98, 4528–4533.
Cumano, A., Ferraz, J., Klaine, M., Di Santo, J., and Godin, I. (2001) Intraembryonic, but not yolk sac hematopoietic precursors, isolated before circulation, provide long-term multilineage reconstitution. Immunity 15, 477–485.
de Bruijn, M., Ma, X., Robin, C., Ottersbach, K., Sanchez, M.-J., and Dzierzak, E. (2002) Hematopoietic stem cells localize to the endothelial cell layer in the midgestation mouse aorta. Immunity 16, 673–683.
North, T., de Bruijn, M., Stacy, T., Talebian, L., Lind, E., Robin, C., et al. (2002) Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. Immunity 16, 661–672.
Matsuoka, S., Tsuji, K., Hisakawa, H., Xu, M.-J., Ebihara, Y., Ishii, T., et al. (2001) Generation of definitive hematopoietic stem cells from murine early yolk sac and paraaortic splanchnopleura by aorta-gonad-mesonephros region-derived stromal cells. Blood 98, 6–12.
Kyba, M., Perlingeiro, R., and Daley, G. Q. (2002) HoxB4 confers definitive lymphoidmyeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors. Cell 109, 29–37.
Yoder, M. and Hiatt, K. (1997) Engraftment of embryonic hematopoietic cells in conditioned newborn recipients. Blood 89, 2176–2183.
Yoder, M., Hiatt, K., and Mukherjee, P. (1997) In vivo repopulating hematopoietic stem cells are present in the murine yolk sac at day 9.0 postcoitus. Proc. Natl. Acad. Sci. USA 94, 6776–6780.
Yoder, M. C., Hiatt, K., Dutt, P., Mukherjee, P., Bodine, D. M., and Orlic, D. (1997) Characterization of definitive lymphohematopoietic stem cells in the day 9 murine yolk sac. Immunity 7, 335–344.
Weissman, I., Papaioannou, V., and Gardner, R. (1978) Fetal hematopoietic origins of the adult hematolymphoid system, in Differentiation of Normal and Neoplastic Hematopoietic Cells (Clarkson, B., Marks, P. A., Till, J. E., eds.), Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp. 33–47.
Toles, J. F., Chui, D. H. K., Belbeck, L. W., Starr, E., and Barker, J. E. (1989) Hemopoietic stem cells in murine embryonic yolk sac and peripheral blood. Proc. Natl. Acad. Sci. USA 86, 7456–7459.
Yoder, M., Cumming, J., Hiatt, K., Mukherjee, P., and Williams, D. (1996) A novel method of myeloablation to enhance engraftment of adult bone marrow cells in newborn mice. Biol. Blood Marrow Transplant. 2, 59–67.
Sands, M. and Barker, J. E. (1999) Percutaneous intravenous injection in neonatal mice. Lab. Ani. Sci. 49, 328–330.
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© 2005 Humana Press Inc., Totowa, NJ
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Johnson, S.A., Yoder, M.C. (2005). Reconstitution of Hematopoiesis Following Transplantation Into Neonatal Mice. In: Baron, M.H. (eds) Developmental Hematopoiesis. Methods in Molecular Medicine, vol 105. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-826-9:095
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DOI: https://doi.org/10.1385/1-59259-826-9:095
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-58829-296-4
Online ISBN: 978-1-59259-826-7
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