Inhibition of histone deacetylase activity induces developmental plasticity in oligodendrocyte precursor cells

摘要: Recently, it was demonstrated that lineage-committed oligodendrocyte precursor cells (OPCs) can be converted to multipotent neural stem-like cells, capable of generating both neurons and glia after exposure bone morphogenetic proteins. In an effort understand control the developmental plasticity OPCs, we developed a high-throughput screen identify novel chemical inducers OPC reprogramming. Using this system, discovered inhibition histone deacetylase (HDAC) activity in OPCs acts as priming event induction plasticity, thereby expanding differentiation potential include neuronal lineage. This conversion found mediated, part, through reactivation sox2 highly reproducible at clonal level. Further, genome-wide expression analysis HDAC inhibitor treatment activated 12 other genes or maintain stem cell state while simultaneously silencing large group lineage-specific genes. series experiments demonstrates global acetylation, induced by inhibition, partially reverse lineage restriction inducing plasticity.