Harnessing pluripotent stem cells as models to decipher human evolution

The study of human evolution, long constrained by a lack of experimental model systems, has been transformed by the emergence of the induced pluripotent stem cell (iPSC) field. iPSCs can be readily established from noninvasive tissue sources, from both humans and other primates; they can be maintained in the laboratory indefinitely, and they can be differentiated into other tissue types. These qualities mean that iPSCs are rapidly becoming established as viable and powerful model systems with which it is possible to address questions in human evolution that were until now logistically and ethically intractable, especially in the quest to understand humans' place among the great apes, and the genetic basis of human uniqueness. In this review, we discuss the key lessons and takeaways of this nascent field; from the types of research, iPSCs make possible to lingering challenges and likely future directions. We provide a comprehensive overview of how the seemingly unlikely combination of iPSCs and explicit evolutionary frameworks is transforming what is possible in our understanding of humanity's past and present.