Demoulin Jean-Baptiste, Enarsson Mia, Larsson Jimmy, Essaghir Ahmed, Heldin Carl-Henrik, Forsberg-Nilsson Karin
MEXP Unit, Christian de Duve Institute of Cellular Pathology, Université catholique de Louvain, B-1200 Brussels, Belgium.
Growth Factors. 2006 Sep;24(3):184-96. doi: 10.1080/08977190600696430.
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 and in cells cultured with PDGF-AA or in the absence of growth factor, which induces differentiation. The genetic program elicited by PDGF-AA (156 significantly regulated genes) was 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, rather than acting solely as an instructing agent for neuronal differentiation. Finally, the transcriptional signature of stem cells grown with FGF-2 included a large number of genes over-expressed in gliomas and a core set of conserved genes periodically expressed during the eukaryote cell cycle.
我们之前已经表明,血小板衍生生长因子AA(PDGF-AA)可刺激神经干细胞中神经元祖细胞的扩增,但无法替代成纤维细胞生长因子2(FGF-2)作为干细胞促分裂原。在本研究中,我们比较了在FGF-2存在下生长的神经干细胞、用PDGF-AA培养的细胞或在无生长因子(诱导分化)条件下培养的细胞中的基因表达。由PDGF-AA引发的基因程序(156个显著调控基因)并非独一无二,而是介于FGF-2培养的干细胞和分化细胞的基因程序之间。这些观察结果与以下假设相符:PDGF-AA诱导神经干细胞部分分化,这些细胞保留增殖能力,而不是仅作为神经元分化的指导因子发挥作用。最后,用FGF-2培养的干细胞的转录特征包括大量在胶质瘤中过度表达的基因以及一组在真核细胞周期中周期性表达的保守核心基因。