Chemical-based epigenetic reprogramming to advance pluripotency and totipotency

Reprogramming technology, breaking the inherent limitations of cellular identity and turning somatic cells into pluripotent cells with more developmental potential, holds great promise for cell therapy and regenerative medicine. Compared with traditional methods based on overexpressing transcription factors, chemical reprogramming with small molecules exhibits substantial advantages in safety and convenience, thus being the leading edge. Over the past decade, a notable focus has been reshaping cellular pluripotency and totipotency using pure small-molecule systems. Here, we provide a concise Review comparing the chemical approaches that have emerged to date and discussing the epigenetic regulatory mechanisms involved in chemical reprogramming. This Review highlights the remarkable potential of small-molecule potions to reformulate cell fate through epigenetic reprogramming and newly discovered actions. We aim to offer insights into chemically controlled cell manipulation and key challenges and future application prospects of chemical reprogramming.