Residual Diploidy in Polyploid Tissues: A Cellular State with Enhanced Proliferative Capacity for Tissue Regeneration?

A major objective of modern biomedical research aims to promote tissue self-regeneration after injury, obviating the need for whole organ transplantation and avoiding mortality due to organ failure. Identifying the population of cells capable of regeneration, alongside understanding the molecular mechanisms that activate that population to re-enter the cell cycle, are two important steps to advancing the field of endogenous tissue regeneration toward the clinic. In recent years, an emerging trend has been observed, whereby polyploidy of relevant parenchymal cells, arising from alternative cell cycles as part of a normal developmental process, is linked to restricted proliferative capacity of those cells. An accompanying hypothesis, therefore, is that a residual subpopulation of diploid parenchymal cells retains proliferative competence and is the major driver for any detected postnatal cell turnover. In this perspective review, we examine the emerging literature on residual diploid parenchymal cells and the possible link of this population to endogenous tissue regeneration, in the context of both heart and liver. We speculate on additional cell types that may play a similar role in their respective tissues and discuss outstanding questions for the field.