The deposition of extracellular matrix (ECM) components by fibroblasts is important for normal organ development and wound healing but also contributes to the pathology of many disease states. To gain insight into the developmental origins of fibroblasts, Yuval Rinkevich, Irving Weissman, Michael Longaker and colleagues (Science doi:10.1126/science.aaa2151; 17 April 2015) performed lineage tracing in mouse dorsal skin and identified a cell population with intrinsic fibrogenic potential. Specifically, they identified a population of cells marked by transient embryonic expression of En1 that migrated from the somites into the dorsal trunk dermis and persisted into adulthood. This En1-positive lineage expressed classical fibroblast markers and colocalized with regions marked by ECM deposition. Following cutaneous wounding, this cell population was closely associated with the ensuing scar tissue and collagen type I expression. The authors also observed similar findings in fibrotic skin regions induced by melanoma or radiation. Furthermore, they identified CD26 as a specific marker of this cell population in adult mice and showed that CD26 inhibition could reduce scarring during wound healing. Altogether, these findings provide valuable insights into fibrogenic cell populations and suggest possible avenues for modulating their activity for therapeutic benefit.