Microarray analysis of striatal embryonic stem cells induced to differentiate by ensheathing cell conditioned media

Abstract

The mammalian central nervous system contains well-defined regions of plasticity in which cells of the aldynoglia phenotype promote neuronal growth and regeneration. Only now are the factors that regulate the production of new cells from multipotential neural precursors (MNP) starting to be identified. We are interested in understanding how differentiation towards the aldynoglia phenotype is controlled, and to study these events we have induced the differentiation of embryonic MNP towards this phenotype in vitro. Accordingly, we have used microarrays to analyze gene expression in three different cell populations: olfactory bulb ensheathing cells (EC), a prototypic aldynoglia cell type; undifferentiated MNP; and MNP differentiated in vitro for 24 hr in EC-conditioned media. The expression profiles identified support the idea that the EC are more closely related to Schwann cells and astrocytes than to oligodendrocytes. Following MNP differentiation, more strongly expressed genes define a neuroglial cell phenotype. RT-PCR confirms that S100a6, Mtmr2, and Col5a were highly expressed by EC, whereas Pou3f3 were more strongly expressed in MNP than in EC, and SafB1 and Mash1 expression were induced in MNP by EC-conditioned media. The profile of gene expression after differentiation suggests that Wnt signaling may be inactivated during this process, while activation of the BMP pathway may be elicited through the BMPr1A. These results provide us with a starting point to study the genes involved in the induction of aldynoglia differentiation from MNP.