<i>Pdgf</i> 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 <i>pdgf-like</i> (<i>pdgfl</i>), in the planarian <i>Schmidtea mediterranea</i>. This gene exhibits inducible expression following missing-tissue injury in a back-and-forth manner between <i>myosin⁺</i> muscular cells and <i>piwi-1⁺</i> stem cells. The dynamic expression of <i>pdgfl</i> is induced through the elevation of reactive oxygen species (ROS) levels and phosphorylated extracellular signal-regulated kinase (pERK) signaling over short distances. Suppression of <i>pdgfl</i> expression impairs the regrowth of essential structures, including the intestine and central nervous system. Evidence on the decrease of <i>notum</i> and <i>sfrp-1</i> at the anterior pole, together with the accumulation of <i>myoD⁺</i>PIWI-1⁺ progenitors, suggests a role of <i>pdgfl</i> in pole muscular cell differentiation. These findings highlight the significant impact of <i>pdgfl</i> in orchestrating the behavior of specific cell types by the regional specificity of this gene expression.