Abstract
With the attractive potential therapeutic uses of both endothelial and hematopoietic cells in medicine, much attention has been focused upon the differentiation of embryonic stem (ES) cells into mature cells of these lineages. In this chapter, we present a culture system that has successfully generated both complex endothelial structures and mature hematopoietic cells from undifferentiated ES cells in vitro. The simplicity of this system allows detailed analyses of factors and developmental steps essential in the generation of vascular structures and mature hematopoietic cell types.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Burdsal, C. A., Damsky, C. H., and Pedersen, R. A. (1993) The role of E-cadherin and integrins in mesoderm differentiation and migration at the mammalian primitive streak. Development 118, 829–844.
Yamaguchi, T. P., Dumont, D. J., Conlon, R. A., Breitman, M. L., and Rossant, J. (1993) flk-1, an flt-related receptor tyrosine kinase is an early marker for endothelial cell precursors. Development 118, 489–498.
Moore, M. A. and Metcalf, D. (1970) 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. 18, 279–296.
Shalaby, F., Rossant, J., Yamaguchi, T. P., Gertsenstein, M., Wu, X. F., Breitman, M. L., and Schuh, A. C. (1995) Failure of blood-island formation and vasculogenesis in Flk1-deficient mice. Nature 376, 62–66.
Mercola, M., Wang, C. Y., Kelly, J., Brownlee, C., Jackson-Grusby, L., Stiles, C., and Bowen-Pope, D. (1990) Selective expression of PDGF A and its receptor during early mouse embryogenesis. Dev. Biol. 138, 114–122.
Risau, W. and Flamme, I. (1995) Vasculogenesis. Annu. Rev. Cell Dev. Biol. 11, 73–91.
Coffin, D. J. and Poole, T. J. (1988) Embryonic vascular development: immunohistological identification of the origin and subsequent morphogenesis of the major vessel primordia in quail embryos. Development 102, 735–748.
Nishikawa, S. I., Nishikawa, S., Kawamoto, H., Yoshida, H., Kizumoto, M., Kataoka, H., and Katsura, Y. (1998) In vitro generation of lymphohematopoietic cells from endothelial cells purified from murine embryos. Immunity 8, 761–769.
North, T., Gu, T.-L., Stacy, T., Wang, Q., Howard, L., Binder, M., et al. (1999) Cbfa2 is required for the formation of intra-aortic hematopoietic clusters. Development 126, 2563–2575.
Vecchi, A., Garlanda, C., Lampugnani, M. G., Resnati, M., Matteucci, C., Stoppacciaro, A., et al. Schnurch, H., Risau, W., Ruco, L., Mantovani A, et al (1994) Monoclonal antibodies specific for endothelial cells of mouse blood vessels. Their application in the identification of adult and embryonic endothelium. Eur. J. Cell Biol. 63, 247–254.
Young, P. E., Baumhueter, S., and Lasky, L. A. (1995) The sialomucin CD34 is expressed on hematopoietic cells and blood vessels during murine development. Blood 85, 96–105.
Petrenko, O., Beavis, A., Klaine, M., Kittappa, R., Godin, I., and Lemischka, I. R. (1999) The molecular characterization of the fetal stem cell marker AA4. Immunity 10, 691–700.
Nishikawa, S. I., Nishikawa, S., Fraser, S., Fujimoto, T., Yoshida, H., Hirashima, M., and Ogawa, M. A model for embryonic development of hemopoieitic stem cells through endothelial cells, in Developmental biology of the hematopoietic system. (Zon, L. ed.) Oxford Univ. Press, Oxford, UK, in press.
Risau, W., Sariola, H., Zerwes, H. G., Sasse, J., Ekblom, P., Kemler, R., and Doetschman, T. (1988) Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies. Development 102, 471–478.
Wiles, M. V. and Keller, G. (1991) Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture. Development 111, 259–267.
Schmitt, R. M., Bruyns, E. and Snodgrass, H. R. (1991) Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression. Genes Dev. 5, 728–740.
Burkert, U., von Ruden, T., and Wagner, E. F. (1991) Early fetal hematopoietic development from in vitro differentiated embryonic stem cells. New Biol. 3, 698–708.
Vittet, D., Prandini, M. H., Berthier, R., Schweitzer, A., Martin-Sisteron, H., Uzan, G., and Dejana, E. (1996) Embryonic stem cells differentiate in vitro to endothelial cells through successive maturation steps. Blood 88, 3424–3231.
Kabrun, N., Buhring, H. J., Choi, K., Ullrich, A., Risau, W., and Keller, G. (1997) Flk1 expression defines a population of early embryonic hematopoietic precursors. Development 124, 2039–2048.
Nishikawa, S.-I., Nishikawa, S., Hirashima, M., Matsuyoshi, N., and Kodama, H. (1998) Progressive lineage analysis by cell sorting and culture identifies FLK1+VE-cadherin+ cells at a diverging point of endothelial and hemopoietic lineages. Development 125, 1747–1757.
Gory, S., Vernet, M., Laurent, M., Dejana, E., Dalmon, J., and Huber, P. (1999) The vascular endothelial-cadherin promoter directs endothelial-specific expression in transgenic mice. Blood 93, 184–192.
Hirashima, M., Kataoka, H., Nishikawa, S., Matsuyoshi, N., and Nishikawa, S.-I. (1999) Maturation of embryonic stem cells into endothelial cells in an in vitro model of vasculo-genesis. Blood 93, 1253–1263.
Kodama, H., Nose, M., Yamaguchi, Y., Tsunoda, J., Suda, T., Nishikawa, S., and Nishikawa, S.-I. (1992) In vitro proliferation of primitive hemopoietic stem cells supported by stromal cells: evidence for the presence of a mechanism(s) other than that involving c-kit receptor and its ligands. J. Exp. Med. 176, 351–361.
Nakano, T., Kodama, H., and Honjo, T. (1994) Generation of lymphohematopoietic cells from embryonic stem cells in culture. Science 265, 1098–1101.
Kessel, J. and Fabian, B. (1987) Inhibitory and stimulatory influences on mesodermal erythropoiesis in the early chick blastoderm. Development 101, 45–49.
Robertson, E., Bradley, A., Kuehn, M., and Evans, M. (1986) Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector. Nature 323, 445–448.
Kataoka, H., Takakura, N., Nishikawa, S., Tsuchida, K., Kodama, H., Kunisada, T., et al. (1997) Expressions of PDGF receptor alpha, c-Kit and Flk1 genes clustering in mouse chromosome 5 define distinct subsets of nascent mesodermal cells. Dev. Growth Differ. 39, 729–740.
Shirayoshi, Y., Nose, A., Iwasaki, K., and Takeichi, M. (1986) N-linked oligosaccharides are not involved in the function of a cell-cell binding glycoprotein E-cadherin. Cell Struct. Funct. 11, 245–252.
Matsuyoshi, N., Toda, K., Horiguchi, Y., Tanaka, T., Nakagawa, S., Takeichi, M., and Imamura, S. (1997) In vivo evidence of the critical role of cadherin-5 in murine vascular integrity. Proc. Assoc. Am. Physicians 109, 362–371.
Ogawa, M., Kizumoto, M., Nishikawa, S., Fujimoto, T., Kodama, H., and Nishikawa, S.-I. (1999) Expression of alpha4-integrin defines the earliest precursor of hemopoietic cell lineage diverged from endothelial cells. Blood 93, 1168–1177.
Cho, S. K., Webber, T. D., Carlyle, J. R., Nakano, T., Lewis, S. M., and Zuniga-Pflucker, J. C. (1999) Functional characterization of B lymphocytes generated in vitro from embryonic stem cells. Proc. Natl. Acad. Sci. USA 96, 9797–9802.
Sudo, T., Nishikawa, S., Ogawa, M., Kataoka, H., Ohno, N., Izawa, A., et al. (1995) Functional hierarchy of c-kit and c-fms in intramarrow production of CFU-M. Oncogene 11, 2469–2476.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Fraser, S.T., Ogawa, M., Nishikawa, S., Nishikawa, SI. (2002). Embryonic Stem Cell Differentiation as a Model to Study Hematopoietic and Endothelial Cell Development. In: Turksen, K. (eds) Embryonic Stem Cells. Methods in Molecular Biology™, vol 185. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-241-4:71
Download citation
DOI: https://doi.org/10.1385/1-59259-241-4:71
Publisher Name: Springer, Totowa, NJ
Print ISBN: 978-0-89603-881-3
Online ISBN: 978-1-59259-241-8
eBook Packages: Springer Protocols