The gene expression profile of PDGF-treated neural stem cells corresponds to partially differentiated neurons and glia

Understanding and controlling stem cell differentiation in vitro is critical for the development of stem cell-based therapies. We have previously shown that platelet-derived growth factor AA (PDGF-AA) stimulates the expansion of neuronal progenitors from neural stem cells, but is unable to replace fibroblast-growth factor 2 (FGF-2) as a stem cell mitogen. In the present study, we compared gene expression in neural stem cells that were grown in the presence of FGF-2 to that of cells cultured with PDGF-AA or in the absence of growth factor, which induces differentiation. Most of the transcripts enriched in FGF-2-treated cells were connected to cell division (70%) and showed limited overlap with previously described stem cell transcriptional signatures. PDGF-AA significantly regulated 156 genes, 146 of which were also modified by differentiation in the absence of growth factor. The latter condition affected the expression of 153 additional genes which were regulated less than two fold by PDGF-AA. Among the genes induced by differentiation was the PDGF-A gene itself, suggesting that in the absence of exogenously added growth factors, cells make their own PDGF-AA in an autocrine manner. In addition, we identified several poorly characterized transcripts that were highly regulated and may play a role in stem cell differentiation. Our results suggest that the genetic program elicited by PDGF-AA is not unique, but an intermediate between the ones of FGF-2-cultured stem cells and differentiated cells. These observations are compatible with the hypothesis that PDGF-AA induces a partial differentiation of neural stem cells, which retain the ability to proliferate. Keywords: treatment comparison Neural stem cells were grown in the presence of FGF2 (reference), in the absence of growth factor, which induces differentiation, or in the presence of PDGF for 12 hours or 6 days. Hybridizations were carried out in quadrulicates from at least two independent RNA preparations. Cy3 and cy5 dyes were swapped in two out of four replicates.