Embryonic stem cells of the non-human primate Callithrix jacchus can be differentiated into definitive endoderm by Activin-A but not IDE-1/2.

Pluripotent stem cells hold great promise for regenerative medicine, due to their unlimited self-renewal potential and the ability to differentiate into all somatic cell types. Differences between the rodent disease models and the situation in humans can be narrowed down with non-human primate models. The common marmoset monkey (Callithrix jacchus) is an interesting model for biomedical research because these animals are easy to breed, get relatively old (≤ 13 years), are small in size, are relatively cost-effective and have a high genetic proximity to the human. In particular, diseases of the liver and pancreas are interesting for cell replacement therapies but the in vitro differentiation of ESCs into the definitive endoderm germ layer is still a demanding task. Membrane-permeable, chemically defined small molecules can possibly replace recombinant growth factors used in most directed differentiation protocols. However, the potent small molecules IDE-1 and IDE-2 were not able to induce definitive endoderm-like cells when ESCs from the common marmoset were treated with these compounds, whereas the recombinant growth factor Activin A could force the differentiation into this lineage. Our results indicate that ESCs from the common marmoset are less sensitive or even insensitive to these small molecules. Thus, differences between the species of human ESCs and ESCs of this non-human primate might be a useful model to further evaluate the exact mode of action of these compounds.