The conversion of differentiated cells to a pluripotent state through somatic cell nuclear transfer provided the first unequivocal evidence that differentiation was reversible. In more recent times, introducing a combination of key transcription factors into terminally differentiated mammalian cells was shown to drive their conversion to induced pluripotent stem cells (iPSCs). These discoveries were transformative, but the relatively slow speed (2–3 weeks) and low efficiency of reprogramming (0.1–1%) made deciphering the underlying molecular mechanisms difficult and complex. Cell fusion provides an alternative reprogramming approach that is both efficient and tractable, particularly when combined with modern multi-omics analysis of individual cells. Here we review the history and the recent advances in cell–cell fusion that are enabling a better understanding cell fate conversion, and we discuss how this knowledge could be used to shape improved strategies for regenerative medicine.

通过体细胞核移植将分化细胞转化为多能状态提供了第一个明确的证据，证明分化是可逆的。最近，将关键转录因子的组合引入终末分化的哺乳动物细胞被证明可以推动它们转化为诱导多能干细胞 (iPSC)。这些发现是变革性的，但相对较慢的速度（2-3 周）和低效率的重编程（0.1-1%）使得破译潜在的分子机制变得困难和复杂。细胞融合提供了一种有效且易于处理的替代重编程方法，特别是在与单个细胞的现代多组学分析相结合时。