Positional information modulates transient regeneration-activated cell states during vertebrate appendage regeneration

Summary Injury is a common occurrence in the life of organisms. Because the extent of damage cannot be predicted, injured organisms must determine how much tissue needs to be restored. It is known that amputation position determines the regeneration speed of amputated appendages in regeneration-competent animals. Yet, it is not clear how positional information is conveyed during regeneration. Here, we investigated tissue dynamics in regenerating caudal fins in the African killifish ( Nothobranchius furzeri ). We report position-specific, differential modulation of the spatial distribution, duration, and magnitude of proliferation. Regenerating fins profiled by single cell RNA sequencing identified a Transient Regeneration-Activated Cell State (TRACS) that is amplified to match a given amputation position. We located this TRACS to the basal epidermis and found them to express components and modifiers of the extracellular matrix (ECM). We propose a role for these cells in transducing positional information to the regenerating blastema by remodeling the ECM. Highlights Amputation position changes tissue-wide proliferation response Transcriptional compartmentalization is relative to injury type Regeneration deploys Transient Regeneration-Activated Cell States Prediction: positional information is transduced by ECM changes during regeneration