Abstract
Embryonic stem (ES) cells differentiate efficiently in vitro and give rise to many different somatic cell types. Hematopoietic progenitors present within differentiated ES cells (embryoid bodies, EBs) can be identified by replating EB cells into semisolid media with hematopoietic growth factors. The developmental kinetics of various hematopoietic lineage precursors within EBs and molecular and cellular studies of these cells have suggested that the sequence of events leading to the onset of hematopoiesis within EBs is similar to that found within the mouse embryo. Thus, the in vitro differentiation model of ES cells provides a unique opportunity to study onset mechanisms involved in hematopoietic development.
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References
Smith, A. G., Heath, J. K., Donaldson, D. D., Wong, G. G., Moreau, J., Stahl, M., and Rogers, D. (1988) Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336, 688–690.
Williams, R. L., Hilton, D. J., Pease, S., Willson, T. A., Stewart, C. L., Gearing, D. P., et al. (1988) Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature 336, 684–687.
Bradley, A., Evans, M., Kaufman, M. H., and Robertson, E. (1984) Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature 309, 255–256.
Beddington, R. S. and Robertson, E. J. (1989) An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo. Development 105, 733–737.
Wiles, M. V. and Keller, G. (1991) Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture. Development 111, 259–267.
Keller, G., Kennedy, M., Papayannopoulou, T., and Wiles, M. V. (1993) Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol. Cell Biol. 13, 473–486.
Nakano, T., Kodama, H., and Honjo, T. (1994) Generation of lymphohematopoietic cells from embryonic stem cells in culture. Science 265, 1098.
Potocnik, A. J., Nielsen, P. J., and Eichmann, K. (1994) In vitro generation of lymphoid precursors from embryonic stem cells. EMBO J. 13, 5274–5283.
Risau, W., Sariola, H., Zerwes, H. G., Sasse, J., Ekblom, P., Kemler, R., et al. (1988) Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies. Development 102, 471–478.
Wang, R., Clark, R., and Bautch, V. L. (1992) Embryonic stem cell-derived cystic embryoid bodies form vascular channels: an in vitro model of blood vessel development. Development 114, 303–316.
Vittet, D., Prandini, M. H., Berthier, R., Schweitzer, A., Martin-Sisteron, H., Uzan, G., et al. (1996) Embryonic stem cells differentiate in vitro to endothelial cells through successive maturation steps. Blood 88, 3424–3431.
Yamashita, J., Itoh, H., Hirashima, M., Ogawa, M., Nishikawa, S., Yurugi, T., et al. (2000) Flk 1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature 408, 92–96.
Maltsev, V. A., Rohwedel, J., Hescheler, J., and Wobus, A. M. (1993) Embryonic stem cells differentiate in vitro into cardiomyocytes representing sinusnodal, atrial and ventricular cell types. Mech. Dev. 44, 41–50.
Maltsev, V. A., Wobus, A. M., Rohwedel, J., Bader, M., and Hescheler, J. (1994) Cardiomyocytes differentiated in vitro from embryonic stem cells developmentally express cardiac-specific genes and ionic currents. Circ. Res. 75, 233–244.
Doetschman, T. C., Eistetter, H., Katz, M., Schmidt, W., and Kemler, R. (1985) The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J. Embryol. Exp. Morphol. 87, 27–45.
Drab, M., Haller, H., Bychkov, R., Erdmann, B., Lindschau, C., Haase, H., Morano, I., Luft, F. C., and Wobus, A. M. (1997) From totipotent embryonic stem cells to spontaneously contracting smooth muscle cells: a retinoic acid and db-cAMP in vitro differentiation model. FASEB J. 11, 905–915.
Rohwedel, J., Maltsev, V., Bober, E., Arnold, H. H., Hescheler, J., and Wobus, A. M. (1994) Muscle cell differentiation of embryonic stem cells reflects myogenesis in vivo: developmentally regulated expression of myogenic determination genes and functional expression of ionic currents. Dev. Biol. 164, 87–101.
Bain, G., Kitchens, D., Yao, M., Huettner, J. E., and Gottlieb, D. I. (1995) Embryonic stem cells express neuronal properties in vitro. Dev. Biol. 168, 342–357.
Strubing, C., Ahnert-Hilger, G., Shan, J., Wiedenmann, B., Hescheler, J., and Wobus, A. M. (1995) Differentiation of pluripotent embryonic stem cells into the neuronal lineage in vitro gives rise to mature inhibitory and excitatory neurons. Mech. Dev. 53, 275–287.
Fraichard, A., Chassande, O., Bilbaut, G., Dehay, C., Savatier, P., and Samarut, J. (1995) In vitro differentiation of embryonic stem cells into glial cells and functional neurons. J. Cell Sci. 108, 3181–3188.
Liu, S., Qu, Y., Stewart, T. J., Howard, M. J., Chakrabortty, S., Holekamp, T. F., and McDonald, J. W. (2000) Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation. Proc. Natl. Acad. Sci. USA 97, 6126–6131.
Bagutti, C., Wobus, A. M., Fassler, R., and Watt, F. M. (1996) Differentiation of embryonal stem cells into keratinocytes: comparison of wild-type and beta 1 integrin-deficient cells. Dev. Biol. 179, 184–196.
Dani, C., Smith, A. G., Dessolin, S., Leroy, P., Staccini, L., Villageois, P., et al. (1997) Differentiation of embryonic stem cells into adipocytes in vitro. J. Cell Sci. 110, 1279–1285.
Buttery, L. D., Bourne, S., Xynos, J. D., Wood, H., Hughes, F. J., Hughes, S. P., et al. (2001) Differentiation of osteoblasts and in vitro bone formation from murine embryonic stem cells. Tissue Eng. 7, 89–99.
Kramer, J., Hegert, C., Guan, K., Wobus, A. M., Muller, P. K., and Rohwedel, J. (2000) Embryonic stem cell-derived chondrogenic differentiation in vitro: activation by BMP-2 and BMP-4. Mech. Dev. 92, 193–205.
Kennedy, M., Firpo, M., Choi, K., Wall, C., Robertson, S., Kabrun, N., and Keller, G. (1997) A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature 386, 488–493.
Choi, K., Kennedy, M., Kazarov, A., Papadimitriou, J., and Keller, G. (1998) A common precursor for hematopoietic and endothelial cells. Development 125, 725–732.
Millauer, B., Wizigmann-Voos, S., Schnurch, H., Martinez, R., Moller, N. P., Risau, W., et al. (1993) High affinity VEGF binding and developmental expression suggest flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72, 835–846.
Karasuyama, H. and Melchers, F. (1988) Establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4 or 5, using modified cDNA expression vectors. Eur. J. Immunol. 18, 97–104.
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.
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© 2005 Humana Press Inc., Totowa, NJ
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Choi, K., Chung, Y.S., Zhang, W.J. (2005). Hematopoietic and Endothelial Development of Mouse Embryonic Stem Cells in Culture. In: Baron, M.H. (eds) Developmental Hematopoiesis. Methods in Molecular Medicine, vol 105. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-826-9:359
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DOI: https://doi.org/10.1385/1-59259-826-9:359
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