In 2006, Shinya Yamanaka discovered that adult somatic cells can be reprogrammed into an embryonic-like pluripotent state by delivering transcription factors. These reprogrammed cells, known as induced pluripotent stem (iPS) cells, have the potential to develop into every cell type in the body and are invaluable tools for disease modeling, drug screening, and cell therapy. iPS cells also provide an unprecedented opportunity for discovery in life science, and in Yamanaka’s lab today, researchers continue to use them to investigate the mechanisms for cell fate determination, the reprogramming process, and pluripotency. Work from Yamanaka’s lab has demonstrated that a few transcription factors in combinations can reprogram cell fate from somatic lineages back to a pluripotent state. This groundbreaking work established the field of iPS cell technology, and hundreds of scientists are now trying to bring the technology to patients. Continuing efforts in Yamanaka’s lab to elucidate the mechanisms underlying pluripotency and reprogramming revealed that beyond the action of transcription factors, post-transcriptional regulation is also critical for cell fate determination. For example, they demonstrated that NAT1 (eIF4G2), a translation initiation factor, plays multiple roles in human stem cells depending on differentiation status. Their research addresses complex interactions between transcriptional control and post-transcriptional regulation, and contributes to innovative therapeutic options for patients including gene and cell therapies.