Journal
SCIENCE ADVANCES
Volume 5, Issue 11, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aax7525
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Funding
- National Key Research and Development Program of China [2017YFC1001602, 2017YFA0106300, 2017YFA0102900, 2018YFA0107100, 2016YFA0100300]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16030505]
- National Natural Science Foundation projects of China [U1601227, 31622037, 31631163001, 81570520, 31701281, 31701106, 31601176, 31601088, 31801168, 31900614, 31970709, 81901275]
- Key Research Program of Frontier Sciences, CAS [QYZDB-SSW-SMC001]
- CAS STS Program
- Guangzhou Health Care and Cooperative Innovation Major Project [201704020218, 201604020009]
- Guangdong Province Science and Technology Program [2015TX01R047, 2017B020230005, 2017A020215056, 2017B030314056, 2018A030313825, 2018GZR110103002]
- Guangzhou Science and Technology Program [201707010178, 201807010067]
- Yangtze River Scholar Bonus Schemes
- CAS Youth Innovation Promotion Association
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Metabolic reprogramming has emerged as a key regulator of cell fate decisions. Roles of glucose and amino acid metabolism have been extensively documented, whereas lipid metabolism in pluripotency remains largely unexplored. Using a high-coverage lipidomics approach, we reveal dynamic changes in phospholipids occurring during reprogramming and show that the CDP-ethanolamine (CDP-Etn) pathway for phosphatidylethanolamine (PE) synthesis is required at the early stage of reprogramming. Mechanistically, the CDP-Etn pathway inhibits NF-kappa B signaling and mesenchymal genes in a Pebp1-dependent manner, without affecting autophagy, resulting in accelerated mesenchymal-to-epithelial transition (MET) and enhanced reprogramming. Furthermore, PE binding to Pebp1 enhances the interaction of Pebp1 with IKK alpha/beta and reduces the phosphorylation of IKK alpha/beta. The CDP-Etn-Pebp1 axis is associated with EMT/MET in hepatocyte differentiation, indicating that Etn/PE is a broad-spectrum MET/EMT-regulating metabolite. Collectively, our study reveals an unforeseen connection between phospholipids, cell migration, and pluripotency and highlights the importance of phospholipids in cell fate transitions.
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