期刊
STEM CELLS INTERNATIONAL
卷 2017, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2017/2493752
关键词
-
资金
- Ministry of Science and Technology [NSC-100-2314-B-002-004-MY3]
SDF-1 and its primary receptor, CXCR4, are highly expressed in the embryonic central nervous system( CNS) and play a crucial role in brain architecture. Loss of SDF-1/CXCR4 signaling causes abnormal development of neural stem/progenitor cells ( NSCs/NPCs) in the cerebellum, hippocampus, and cortex. However, the mechanism of SDF-1/CXCR4 axis in NSCs/NPCs regulation remains unknown. In this study, we found that elimination of SDF-1/CXCR4 transduction caused NSCs/NPCs to lose their stemness characteristics and to encounter neurogenic differentiation. Moreover, Notch and RE1 silencing transcription factor ( REST) both play an essential role in NSCs/NPCs maintenance and neuronal differentiation and were dramatically downregulated following SDF-1/CXCR4 cascade inhibition. Finally, we demonstrated that the expression of achaete-scute homolog 1 ( Ascl1), a proneural gene, and p27, an antiproliferative gene, were significantly increased after genetic elimination of SDF-1 alleles. Our results support that the loss of functional SDF-1/CXCR4 signaling pathway in NSCs/NPCs induces exit of cell cycle and promotes premature neural differentiation.
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