the CDP-Etn pathway accelerates mesenchymal-to-epithelial transition in somatic cell reprogramming

Metabolic reprogramming has emerged as key regulators of cell fate decisions. Whereas the glucose and amino acid metabolism have been extensively documented, the roles of lipid metabolism in pluripotency remain largely unexplored. Here, we report that the CDP-Ethanolamine (CDP-Etn) pathway for phosphatidylethanolamine synthesis is required for somatic cell reprogramming at the early stage. Mechanistically, the CDP-Etn pathway inhibits NF-?B signaling and mesenchymal genes in a Pebp1 dependent manner, resulting in accelerated mesenchymal-to-epithelial transition and enhanced reprogramming. In addition, we show that phospholipids are critical for the growth of mESC though without effects on pluripotency. Our study reveals an unforeseen connection between phospholipids, cell migration and pluripotency and highlights the importance of phospholipids in cell fate transitions. Overall design: We inhibited the CDP-Etn pathway by shRNAs (shEtnk1/2 or shPcyt2) or Etn deprivation in MEFs undergoing reprogramming and performed RNA-seq. We also knocked down Pebp1 using shPebp1 with or without Etn and performed RNA-seq to determine whether Etn functions in a Pebp1-dependent manner.