The Dynamic Proteome of Oligodendrocyte Lineage Differentiation Features Planar Cell Polarity and Macroautophagy Pathways

Generation of oligodendrocytes (OLs) is a sophisticated multistep process, mechanistic underpinnings of which are not fully understood and demand further investigation. To systematically profile proteome dynamics during human embryonic stem cell (hESC) differentiation into OLs, we applied in-depth quantitative proteomics at different developmental stages and monitored changes in protein abundance using a multiplexed tandem mass tag (TMT) based proteomics approach. Findings: Our proteome data provided a comprehensive protein expression profile that highlighted specific expression clusters based on the protein abundances over the course of human OL lineage differentiation. The proteome profile of OL lineage cells revealed 378 proteins that were specifically up-regulated only in one differentiation stage. In addition, comparative pairwise analysis of differentiation stages demonstrated that abundances of 352 proteins differentially changed between consecutive differentiation time points. Our results highlighted the eminence of the planar cell polarity (PCP) signaling and autophagy (particularly macroautophagy) in the progression of OL lineage differentiation