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10 Embryonic Stem Cells

Austin Smith


Embryonic stem (ES) cells are pluripotent stem cell lines derived directly from early mouse embryos without use of immortalizing or transforming agents. They can be propagated as homogeneous stem cell cultures and expanded without apparent limit. Unusually among established cell lines, ES cells maintain a stable euploid karyotype. Yet more remarkably, ES cells retain the character of embryo founder cells, even after prolonged culture and extensive manipulation. Thus, they are able to reintegrate fully into embryogenesis when returned to the early embryo. Chimeric mice can be produced in which ES cell descendants are represented among all cell types, including functional gametes. ES cells are also readily amenable to sophisticated genome engineering, in particular via homologous recombination. These properties are widely exploited to introduce gene knock-outs and other precise genetic modifications into the mouse germ line.

The ability to propagate pluripotent ES cells presents unique opportunities for experimental analysis of gene regulation and function during self-renewal, cell commitment, and differentiation. The combination of intrinsic and extrinsic factors that maintain developmental identity and potency is beginning to be defined. Progress is also being made toward understanding and controlling lineage- and/or cell-type-specific differentiation of ES cells in vitro. When harnessed effectively, ES cell differentiation can provide defined cell populations for pharmacological testing and cellular transplantation. Generation of ES cell equivalents from other species, most particularly human, is now anticipated for realization of the full power of ES cell technologies both as research tools and, ultimately, as cell therapy reagents.


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