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干细胞因子和粒细胞集落刺激因子促进神经干细胞向神经元谱系的定向分化。

Stem cell factor and granulocyte colony-stimulating factor promote neuronal lineage commitment of neural stem cells.

机构信息

Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.

出版信息

Differentiation. 2012 Jan;83(1):17-25. doi: 10.1016/j.diff.2011.08.006. Epub 2011 Oct 5.

DOI:10.1016/j.diff.2011.08.006
PMID:22099173
Abstract

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.

摘要

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。

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