In vitro breeding: Application of embryonic stem cells to animal production

Abstract

Pluripotent stem cells (PSCs) are cells capable of self-renewing and differentiating into any of the three primary germ layers under certain conditions. Because of their ability to survive in vitro and their pluripotency, they have become the main cell source for innovative cell therapies, pharmaceutical screening and testing procedures and other biotechnological applications, including genetic engineering. Genetically-modified PSCs can be easily screened for and used to generate embryonic chimeras that transmit the modified genome to the next generation. As example, PSCs have been widely used to generate transgenic mice models through blastocyst complementation, where modified PSCs are injected into blastocysts. This strategy, however, is not practical in livestock species, where development and biological processes take much longer and where mothers give rise to only one offspring at a time. Establishing homozygous modified founders by this method would take years, especially if more than one mutation is involved. Nonetheless, other alternatives can be evaluated nowadays to produce genetically modified embryos in livestock. For instance, PSCs have been shown to possess a high reprogramming efficiency when used as nuclei donors in somatic cell nuclear transfer (SCNT), resulting in fertile clones (Eggan et al., 2001; Kou et al., 2010), hence modified PSCs could constitute a good starting point for getting improved clones. Because of the multiple advantages these cells offer in terms of production of genetically modified animals, a very special interest for deriving PSCs in livestock species has arisen, although success up to date has been limited. Throughout the following sections, we will show the current state-of-the-art in the matter of embryonic stem cells and their differentiation into germ cells in mammalian livestock species. This is important to present a new methodology for genetic improvement of livestock, which is going to greatly decrease the generational interval and increase the intensity of selection by combining the advantages of modern techniques of cell biology with genomic selection.