Planarian progenitor responses to injury are not specific to missing tissue identity.

Regeneration is the process by which organisms replace lost body parts. How cell-type production is tailored to match missing-tissue identity is a central problem of regeneration. Here, we investigated the specificity of planarian stem-cell responses to the identity of missing tissues following injury. Proximal injury not affecting the mature tissue nonetheless drives increased cell incorporation into brain neurons, ventral nerve cords, and pharynx muscle and neurons. Following direct injury, there is spatially imprecise amplification of cell incorporation into peripheral neurons relative to the wound, and decreased cell incorporation into body-wall muscle distally in favor of increased incorporation at the wound. By contrast, essentially no stem-cell division contributes to initial epidermal regeneration, instead post-mitotic progenitors supply the wound. Amplification of epidermal incorporation following injury does occur weeks after injury, including to uninjured regions. These results indicate that the identity of the missing mature tissue is not required in determining the stem-cell response to injury. We suggest that planarian regeneration specificity involves in large part a combination of ongoing cell turnover, wound-associated increased stem cell division, and spatially broad neoblast specification zones.