Histone deacetylase inhibitor promotes differentiation of embryonic stem cells into neural cells in adherent monoculture

Abstract

Background Embryonic stem (ES) cells poss unlimited self-renewal capacity and the ability to differentiate into cell of all three germ layers in vitro. Induced differentiation of ES cells to neural lineage cells has great potential in basic study of neurogenesis and regeneration therapy of neurodegenerative diseases. Histone deacetylase (HDAC) inhibitors enhance histone acetylation so that globularly activate gene expression and may initiate multilineage differentiation. In this study, we aimed to develop a method to induce the differentiation of ES cells to neural cells combining HDAC inhibition and neural cell selection. Methods In this study, we used HDAC inhibitor sodium butyrate (NaB) to induce the differentiation of mouse embryonic stem cells to neural cells through monolayer culture. After differentiation initiation by histone deacetylase inhibitor sodium butyrate, neural cells were induced and selected with a serum free culture system. Results Homogeneous neurons without glial cells demonstrated by molecular marker expression were differentiated with the method. The resultant neurons were excitable. Conclusion The method combined differentiation induction effect of HDAC inhibitors and selective culture system to derive neural cells from ES cells, and implied the involvement of epigenetic regulation in neural differentiation.