The reprogramming of somatic cells to an induced pluripotent stem (iPS) cell state requires profound signalling, transcriptional and epigenetic rewiring. Similarly, the regeneration of mammalian tissues involves significant changes in cell behaviour and the transient acquisition of functions mediate the repair of damage and which can be thought of as adaptive cell reprogramming. We previously demonstrated that protein citrullination is induced upon the introduction of the Yamanaka transcription factors into somatic cells, where it precedes and mediates their reprogramming. We have since found that the induction of citrullination is a general, evolutionarily conserved feature of tissue regeneration. The cells that activate citrullination are mutually exclusive with the iPS or tissue stem cells, suggesting that they act as “active bystanders” that mediate reprogramming in a non-cell-autonomous manner. The bystander cells release citrullinated chromatin to the extracellular space, in a process akin to Neutrophil Extracellular Traps. Blocking of extracellular chromatin components reduces reprogramming, as does pharmacological interference with extracellular chromatin-sensing signalling pathways, while ablation of the citrullinating enzyme PADI4 impairs regeneration. Our findings open a new research avenue into the study of citrullination and extracellular chromatin as a cell communication mechanism that mediates cell fate transitions.