Fatty acid synthesis is critical for stem cell pluripotency via promoting mitochondrial fission |
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| Authors: | Lihua Wang Tong Zhang Lin Wang Yongping Cai Xiuying Zhong Xiaoping He Lan Hu Shengya Tian Mian Wu Lijian Hui Huafeng Zhang Ping Gao |
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| Affiliation: | 1. CAS Key Laboratory of Innate Immunity and Chronic Disease, Hefei National Laboratory for Physical Sciences at Microscale, Innovation Center for Cell Signaling Network, School of Life Science, University of Science and Technology of China, Hefei, China;2. Department of Pathology, School of Medicine, Anhui Medical University, Hefei, China;3. Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy for Sciences, Shanghai, China |
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| Abstract: | Pluripotent stem cells are known to display distinct metabolic phenotypes than their somatic counterparts. While accumulating studies are focused on the roles of glucose and amino acid metabolism in facilitating pluripotency, little is known regarding the role of lipid metabolism in regulation of stem cell activities. Here, we show that fatty acid (FA) synthesis activation is critical for stem cell pluripotency. Our initial observations demonstrated enhanced lipogenesis in pluripotent cells and during cellular reprogramming. Further analysis indicated that de novo FA synthesis controls cellular reprogramming and embryonic stem cell pluripotency through mitochondrial fission. Mechanistically, we found that de novo FA synthesis regulated by the lipogenic enzyme ACC1 leads to the enhanced mitochondrial fission via (i) consumption of AcCoA which affects acetylation‐mediated FIS1 ubiquitin–proteasome degradation and (ii) generation of lipid products that drive the mitochondrial dynamic equilibrium toward fission. Moreover, we demonstrated that the effect of Acc1 on cellular reprogramming via mitochondrial fission also exists in human iPSC induction. In summary, our study reveals a critical involvement of the FA synthesis pathway in promoting ESC pluripotency and iPSC formation via regulating mitochondrial fission. |
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| Keywords: | Acc1 FA synthesis Fis1 mitochondrial fission pluripotency |
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