TY - JOUR
T1 - SDF-1/CXCR4 Signaling Maintains Stemness Signature in Mouse Neural Stem/Progenitor Cells
AU - Ho, Shih Yin
AU - Ling, Thai Yen
AU - Lin, Hsing Yu
AU - Liou, Jeffrey Tsai Jui
AU - Liu, Fei Chih
AU - Chen, I. Chun
AU - Lee, Sue Wei
AU - Hsu, Yu
AU - Lai, Dar Ming
AU - Liou, Horng Huei
N1 - Publisher Copyright:
© 2017 Shih-Yin Ho et al.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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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U2 - 10.1155/2017/2493752
DO - 10.1155/2017/2493752
M3 - Article
AN - SCOPUS:85017110978
SN - 1687-966X
VL - 2017
JO - Stem Cells International
JF - Stem Cells International
M1 - 2493752
ER -