Inhibition of class II histone deacetylase blocks proliferation and promotes neuronal differentiation of the embryonic rat neural progenitor cells

摘要

Neural precursor cells (NPCs), which are capable of self-renewing, migrating to specific sites, and differentiating into the three main CNS lineages, neurons, astrocytes and oligodendrocytes, have been used experimentally to repair the damaged nervous system, either by grafting of cells grown in vitro or by activating endogenous NPCs. The grafting of NPCs, however, is limited by its lower viability and undesired glial differentiation. Understanding the mechanism underlying these events, therefore, is essential for the potential future use of NPCs. In the present study, we investigated the role of histone deacetylase (HDAC) inhibition on survival, proliferation, differentiation and migration of the rat NPCs. We observed that NPCs derived from the E14.5 rat brain constitutively expressed both class I and class II HDAC mRNA. Inhibition of HDAC by trichostatin A (TSA) blocked the proliferation, increased neuronal differentiation and decreased astrocyte differentiation of the NPCs. Meanwhile, TSA had no significant effects on survival and migration of the NPCs. Finally, we found that HDAC inhibition regulated proliferation and neuronal differentiation of the NPCs was associated with a reduction of class II and but not class I HDAC transcription. These findings collectively demonstrate that in the situation of not affecting survival and migration, HDAC inhibition may induce more neuronal differentiation.