Embryonic stem cells in cattle

Abstract

Embryonic stem cells (ESCs) were first isolated from mouse embryos over 20 years ago (Evans and Kaufman 1981; Martin 1981). These cells, which are able to selfrenew indefinitely and to differentiate in vitro and in vivo into derivatives of all three germ layers, were initially used to study the differentiation process. Yet, soon after, it became clear that ESCs provided an efficient route for precise modification of the genome by gene targeting. The first mutant mice derived from genetically engineered ESCs were created, opening the doors to a new era of animal transgenesis (Capecchi 1989). The successful isolation and multiple applications of mouse ESC (mESC) resulted in numerous efforts aimed to establish ESCs in other species. Livestock production, for example, would greatly benefit if farm animals ESCs were established, in order to efficiently create genetically modified farm animals bearing improved production traits or increased disease resistances. Furthermore, ESC lines from farm animals such as pigs, sheep or cattle will enable to create transgenic animals for modelling human diseases without some of the limitations from the mouse model, i.e. short life span or a physiology and anatomy very different from humans. Unfortunately, although considerable effort has been exerted to isolate and maintain ESC lines from domestic animals, validated ESC lines in species other that mice and primates are yet to be established. Issues that need to be investigated are many, including the identification of species-specific mechanisms underlying pluripotency and markers (for review, see Keefer et al. 2007). A further hurdle is that most of the current empirical approaches to obtain ESC from farm animals closely followed procedures that were developed in humans and mice. Nevertheless, data extrapolation from these species has produced unsatisfactory results and might have misled researchers from finding the functional pathways that control pluripotency in ungulates