Compared with differentiated somatic cells, pluripotent stem cells have the potential to self-renew and differentiate into various types of somatic cells, and thus have broad application prospects in disease treatment.
Pluripotent stem cells have a unique metabolic phenotype, such as glucose metabolism is more inclined to glycolysis rather than aerobic phosphorylation, metabolic pathway among a variety of amino acids is more inclined to synthetic pathway. However, the role of lipid metabolism network in the maintenance and acquisition of stem cell pluripotency is still poorly understood.
Researchers from the University of Science and Technology of China (USTC) firstly identifies a regulatory pathway among fatty acid synthesis, mitochondrial division and cell fate, which will benefits the clinical research of pluripotent stem cells significantly.
Figure. A working model: FA synthesis is critical for stem cell pluripotency via promoting mitochondrial fission. (Image by GAO Ping, ZHANG Huafeng)
Prof. GAO Ping and Prof. ZHANG Huafeng's group from School of Life Sciences, USTC, found that lipid accumulation was present in embryonic stem cells and in cell reprogramming, which was mainly due to the enhancement of the fatty acid de novo synthesis pathway.
Further mechanism studies have shown that Acc1-mediated fatty acid de novo synthesis pathway promotes mitochondrial cleavage by two mechanisms to finally affect the cell pluripotency: the lipid synthesis pathway consumes intracellular acetylated CoA as a substrate, thereby reducing the ubiquitination degradation caused by acetylation of mitochondrial cleavage protein Fis1; the resulting product fatty acids themselves can promote the mitochondrial dynamic equilibrium to tend to divide.
The study showed that the de novo synthesis of fatty acid can regulate cell pluripotency via affecting mitochondrial fission, and it further confirms that the regulatory pathway is also conserved in the human system.
This study has established a regulatory pathway among fatty acid synthesis, mitochondrial division and cell fate for the first time, which is of great significance for the clinical research of pluripotent stem cells.
The work recently published in the prestigious EMBO Journal entitled “Fatty acid synthesis is critical for stem cell pluripotency via promotingmitochondrial fission” .
The research work received great support from CAI Yongping (Anhui Medical University), HUI Lijian Group (Shanghai Institute of Biochemistry and Cell Biology, China Academy of Sciences) and WU Mian group (School of Life Sciences, USTC). This study was completed with the funding of the Ministry of Science and Technology, the Chinese Academy of Sciences and the National Natural Science Foundation of China.
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