Decoding human chemical reprogramming: mechanisms and principles

Pluripotent stem cells hold great promise as an unlimited resource for regenerative medicine due to their capacity to self-renew and differentiate into various cell types. Chemical reprogramming using small molecules precisely regulates cell signaling pathways and epigenetic states, providing a novel approach for generating human pluripotent stem cells. Since its successful establishment in 2022, human chemical reprogramming has rapidly achieved significant progress, demonstrating its significant potential in regenerative medicine. Mechanistic analyses have revealed distinct molecular pathways and regulatory mechanisms unique to chemical reprogramming, differing from traditional transcription-factor-driven methods. In this review we highlight recent advancements in our understanding of the mechanisms of human chemical reprogramming, with the goal of enhancing insights into the principles of cell fate control and advancing regenerative medicine.