title: Fatty acid synthesis is critical for stem cell pluripotency via promoting mitochondrial fission.
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 thatde novoFA synthesis controls cellular reprogramming and embryonic stem cell pluripotency through mitochondrial fission. Mechanistically, we found thatde novoFA 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.
authors.affiliation: 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.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Medicine, Anhui Medical University, Hefei, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Zhong
authors.affiliation: 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.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: He
authors.affiliation: 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.
authors.forename: Lan
authors.initials: L
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Shengya
authors.initials: S
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Mian
authors.identifier: 0000-0002-2714-0500
authors.initials: M
authors.lastname: Wu
authors.affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy for Sciences, Shanghai, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Hui
authors.affiliation: 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 hzhang22@ustc.edu.cn pgao2@ustc.edu.cn.
authors.forename: Huafeng
authors.identifier: 0000-0001-9923-7531
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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 hzhang22@ustc.edu.cn pgao2@ustc.edu.cn.
authors.forename: Ping
authors.identifier: 0000-0002-6930-7989
authors.initials: P
authors.lastname: Gao
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D063154:Mitochondrial Dynamics; D039904:Pluripotent Stem Cells / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D000105:Acetyl Coenzyme A; C000588423:ACACA protein, human; D000103:Acetyl-CoA Carboxylase
keywords: Acc1; FA synthesis; Fis1; mitochondrial fission; pluripotency