Pdgf mediates a transient regeneration-activated cell state in planarian tissue regeneration

The role of induced gene expression is crucial for tissue regeneration. The transient regenerative cellular state that discriminates between missing-tissue and non-missing-tissue injuries remains to be fully elucidated. In this study, we identified a homolog of Platelet-Derived Growth Factor (PDGF), named pdgf-like (pdgfl), in the planarian Schmidtea mediterranea. This gene exhibits inducible expression following missing-tissue injury in a back-and-forth manner between myosin⁺ muscular cells and piwi-1⁺ stem cells. The dynamic expression of pdgfl is induced through the elevation of reactive oxygen species (ROS) levels and phosphorylated extracellular signal-regulated kinase (pERK) signaling over short distances. Suppression of pdgfl expression impairs the regrowth of essential structures, including the intestine and central nervous system. Evidence on the decrease of notum and sfrp-1 at the anterior pole, together with the accumulation of myoD⁺PIWI-1⁺ progenitors, suggests a role of pdgfl in pole muscular cell differentiation. These findings highlight the significant impact of pdgfl in orchestrating the behavior of specific cell types by the regional specificity of this gene expression.