Exposure to valproic acid increases a subset of chromaffin progenitor cells within chromospheres

Abstract

Chromaffin cells and sympathetic neurons derive from a common sympathoadrenal progenitor cell. Recently we demonstrated the existence of chromaffin progenitor cells in the adult adrenal and their capacity to derive dopaminergic neurons in vitro. Valproic acid (VA) is a histone deacetylase inhibitor that stimulates extended growth of neural stem cells. Here, we discuss the potential use of VA in improving proliferation of bovine medullary chromaffin progenitor cells. Similar to neural stem cells, chromaffin progenitors were cultured as free-floating spheroid clusters, chromospheres (CS). Treatment with VA increased proliferation of chromaffin progenitors and their enrichment within CS accompanied by an increased expression of neural progenitor markers such as nestin, Mash1, Sox1/10, Hes1. Accumulation of cells in S-phase and their increase in G2 cell cycle phase was pronounced after treatment with VA. Our findings indicate common molecular mechanisms that control maintenance of neural and chromaffin progenitors.