Mitochondrial state determines functionally divergent stem cell population in planaria. Schmidtea mediterranea strain:CIW4

Mitochondrial state changes were shown to be critical for the stem cell function. However, the variation in the mitochondrial content in the stem cell population and its implication on the differentiation was poorly understood. Here using cellular and molecular studies, we show that the pluripotent neoblast has low mitochondrial mass compared to its progenitors. Further, the increased mitochondrial mass in the progenitors correlated with high OxPhos activity and the inhibition of its activity in the cultured neoblast resulted in increased stemness. Transplantation experiments functionally validated neoblast with low mitochondrial mass as a true pluripotent stem cell. In summary, we show that low mitochondrial mass is a hall mark of pluripotent stem cells in planaria and the differences in the mitochondrial mass can be used as a marker to isolate neoblast from different cycle stages (G0/G1, S/G2/M) for functional characterization. Further our study also showed that the change in the mitochondrial state was a deterministic factor for stem cell function, a feature conserved across the metazoans.