Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
Differentiation. 2012 Jan;83(1):17-25. doi: 10.1016/j.diff.2011.08.006. Epub 2011 Oct 5.
Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) were originally discovered as growth factors for hematopoietic stem cells (HSCs). It has been well defined that SCF and G-CSF contribute to regulation of lineage commitment for HSCs. However, little is known about whether SCF and G-CSF play roles in the determination and differentiation of neural stem cells (NSCs). Here we demonstrate the novel function of SCF and G-CSF in controlling cell cycle and cell fate determination of NSCs. We also observe that SCF and G-CSF promote neuronal differentiation and inhibit astroglial differentiation at the early stage of differentiation. In addition, our research data reveal that SCF in combination with G-CSF has a dual function in promoting cell cycle exit and directing neuronal fate commitment at the stage of NSC dividing. This coordination effect of SCF+G-CSF on cell cycle arrest and neuronal differentiation is through enhancing neurogenin 1 (Ngn1) activity. These findings extend current knowledge regarding the role of SCF and G-CSF in the regulation of neurogenesis and provide insights into the contribution of hematopoietic growth factors to brain development and remodeling.
干细胞因子 (SCF) 和粒细胞集落刺激因子 (G-CSF) 最初被发现是造血干细胞 (HSCs) 的生长因子。已经明确的是,SCF 和 G-CSF 有助于调节 HSCs 的谱系定向。然而,对于 SCF 和 G-CSF 是否在神经干细胞 (NSCs) 的决定和分化中发挥作用,人们知之甚少。在这里,我们证明了 SCF 和 G-CSF 在控制 NSCs 的细胞周期和细胞命运决定中的新功能。我们还观察到,SCF 和 G-CSF 在分化的早期促进神经元分化并抑制星形胶质细胞分化。此外,我们的研究数据表明,SCF 与 G-CSF 联合具有在 NSC 分裂阶段促进细胞周期退出和指导神经元命运决定的双重功能。SCF+G-CSF 对细胞周期阻滞和神经元分化的协调作用是通过增强神经基因 1 (Ngn1) 的活性。这些发现扩展了关于 SCF 和 G-CSF 在神经发生调节中的作用的现有知识,并为造血生长因子对大脑发育和重塑的贡献提供了新的见解。