Methods to Generate Chimeric Mice from Embryonic Stem Cells

A chimera is an animal that has two or more populations of genetically distinct cells that originated in different embryos, fetuses, or individuals of the same or different species. During recent decades, embryos, the inner cell mass (ICM), teratocarcinoma stem cells, embryonal carcinoma stem cells, embryonic stem (ES) cells (ESCs), primordial germ cells, spermatogonial stem cells, extraembryonic endoderm (XEN) cells (Kunath et al., 2005), induced pluripotent stem cells (iPSCs) (Boland et al., 2009; Kang et al., 2009; Takahashi & Yamanaka, 2006; Zhao et al., 2009), epiblast stem cells (EpiSCs) (Brons et al., 2007; Tesar et al., 2007), and other cells have been used to generate chimeric embryos that can develop into chimeras once transferred to a foster mother. To date, three methods can be applied to produce ESC-derived chimeric embryos: (1) aggregation, (2) microinjection, and (3) coculture. This review uses mouse ES cells as an example to describe and compare existing methods for generating chimeric embryos.