Of mice and men: the riddle of tubular regeneration

Abstract

Regeneration can occur through multiple distinct mechanisms, such as pluripotent stem cells, lineage-committed progenitors or dedifferentiation. The respective contribution of each of these regenerative strategies in every organ or tissue may be different. Recent results indicate that dedifferentiation contributes less than previously thought, and that stem or progenitor cells seem to be the main drivers of regenerative processes. Our views of regeneration in the kidney are undergoing the same process of revision. Indeed, studies in humans have established the existence of a scattered population of tubular progenitors in the adult kidney. Renal progenitors have been discovered also in other animal classes such as fish and insects. In contrast, in rodents a tubular progenitor phenotype seems to be induced only after tubular injury, suggesting some differences may exist. Is this difference really related to a distinct regenerative strategy or is it simply a matter of the type and modality of cellular markers expressed? It may also be possible that progenitor cells, as well as tubular cell dedifferentiation, act in concert to allow regeneration of a complex organ like the adult mammalian kidney, as recently proposed also for the liver. Further studies are needed to resolve the riddle of tubular regeneration. However, beyond the controversial results obtained from humans and rodents, identification of tubular progenitors in humans can move the field forward and provide a novel perspective for understanding tubular regeneration.