Mitochondrial state determines functionally divergent stem cell population in planaria

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.

已有研究表明，线粒体状态变化对干细胞功能至关重要。然而，此前学界对于干细胞群体中线粒体含量的差异及其对细胞分化的影响，认知仍较为匮乏。本研究通过细胞与分子生物学实验证实，多能未分化细胞（neoblast）的线粒体质量相较于其祖细胞更低。进一步研究发现，祖细胞中线粒体质量的升高与高氧化磷酸化（OxPhos）活性呈正相关；而抑制培养中neoblast细胞的氧化磷酸化活性，则可增强其干细胞干性。移植实验从功能层面验证，线粒体质量较低的neoblast细胞即为真正的多能干细胞。综上，本研究表明，低线粒体质量是涡虫（planaria）多能干细胞的标志性特征；而线粒体质量的差异可作为分离不同细胞周期阶段（G0/G1、S/G2/M）neoblast细胞的标志物，用于后续功能表征。此外，本研究还证实，线粒体状态的变化是决定干细胞功能的关键因素，这一特征在后生动物中具有保守性。