The omnipotent stem cells have unlimited self-replication ability, and can differentiate into all types of somatic cells, and then develop into complete organisms. In 2006, Yamanaka et al. successfully transformed differentiated cells into induced pluripotent stem cells (iPS cells) through somatic cell reprogramming. In 2009, Zhou Qi's team from the Institute of Animal Sciences of the Chinese Academy of Sciences reported on Nature that mice developed from iPS cells were successfully obtained by using tetraploid compensation technology, which directly confirmed the potential of iPS cells to differentiate into individuals. Interestingly, they also found that apart from fully pluripotent iPS cells, which can develop into individual organisms, somatic cell reprogramming does produce partially pluripotent iPS cells that cannot develop into mature individuals. Since then, although many achievements have been made in the maintenance of stem cell totipotency and regulation of differentiation, the key factors determining the true totipotency of stem cells and their regulatory mechanisms remain unclear.

Recently, Gaoping Research Group of South China University of Technology, Zhou Qi Research Group of Institute of Zoology of Chinese Academy of Sciences and Zhang Huafeng Research Group of China University of Science and Technology jointly published a paper entitled Mitochondrial dynamics is critical for the full pluripotency and embryonic development potential of pluripotent stem cells online, which reveals mitochondria. Dynamic balance plays a decisive role in the development potential of stem cell embryos. By comparing iPS cells that can develop into biological individuals and those that can not develop into individuals, the researchers found that the genes involved in mitochondrial division were abnormally overexpressed in partially totipotent iPS cells, which resulted in short mitochondria and disordered internal structure. Researchers further altered the expression of mitochondrial division-related genes in iPS and ES cells with different developmental potentials, confirming that mitochondrial overdivision affects their differentiation potential in vitro. Importantly, the genetically modified stem cells were implanted into the uterus of surrogate mice, and the tetraploid compensation experiment successfully verified that the stem cells with excessive mitochondrial division could not develop into individual mice. Mechanisms have been found that excessive mitochondrial division increases intracellular calcium levels, which in turn leads to the degradation of beta-Catenin protein by activating CaMKII, thus affecting the differentiation potential of stem cells and embryonic development.

This study reported for the first time the important role of mitochondrial dynamic balance in regulating stem cell totipotency and cell fate determination, deepening the understanding of somatic cell reprogramming and embryonic development, and has great theoretical significance and potential application prospects.

The first author of this paper is Dr. Zhong Xiuying, Medical College of South China University of Technology/Guangzhou First People's Hospital. Professor Gao Ping, Professor Zhou Qi and Professor Zhang Huafeng are co-authors of this paper. The research was supported by the Ministry of Science and Technology, the National Natural Science Foundation of China, the Chinese Academy of Sciences and the Guangdong Provincial Innovation Team.

Thesis link：https://doi.org/10.1016/j.cmet.2018.11.007