Planarian epidermal stem cells respond to positional cues to promote cell type diversity

Successful regeneration requires the formation of appropriate missing cell types. Progenitors of different lineages form the required cell types. However, simply generating lineages is not enough. Cells produced by a particular lineage often have distinct functions depending on their position within the organism. How this occurs is largely unexplored. Here, we used the planarian epidermal lineage to study how the location of adult progenitor cells results in their acquisition of distinct functional identities. We isolated epidermal RNA and identified eight spatially distinct cellular identities that epidermal stem cells can acquire during differentiation. Using single cell RNA sequencing (SCS) of 303 epidermal progenitors we detected the emergence of distinct spatial identities in all stages of differentiation. Strikingly, spatial identities were detected as early in the lineage as the epidermal stem cells, with further pre-patterning occurring in migratory progenitors derived from these stem cells. Our work identified positional signals that activated regionalized transcriptional programs in epidermal stem cells and subsequently promoted cell type diversity in the epidermis.