SDF-1/CXCR4 Signaling Maintains Stemness Signature in Mouse Neural Stem/Progenitor Cells

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. H...

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Main Authors: Shih-Yin Ho, Thai-Yen Ling, Hsing-Yu Lin, Jeffrey Tsai-Jui Liou, Fei-Chih Liu, I-Chun Chen, Sue-Wei Lee, Yu Hsu, Dar-Ming Lai, Horng-Huei Liou
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2017/2493752
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author Shih-Yin Ho
Thai-Yen Ling
Hsing-Yu Lin
Jeffrey Tsai-Jui Liou
Fei-Chih Liu
I-Chun Chen
Sue-Wei Lee
Yu Hsu
Dar-Ming Lai
Horng-Huei Liou
author_facet Shih-Yin Ho
Thai-Yen Ling
Hsing-Yu Lin
Jeffrey Tsai-Jui Liou
Fei-Chih Liu
I-Chun Chen
Sue-Wei Lee
Yu Hsu
Dar-Ming Lai
Horng-Huei Liou
author_sort Shih-Yin Ho
collection DOAJ
description 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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institution Kabale University
issn 1687-966X
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series Stem Cells International
spelling doaj-art-4e9b5e07b2a442148afc530954a882862025-02-03T01:10:16ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/24937522493752SDF-1/CXCR4 Signaling Maintains Stemness Signature in Mouse Neural Stem/Progenitor CellsShih-Yin Ho0Thai-Yen Ling1Hsing-Yu Lin2Jeffrey Tsai-Jui Liou3Fei-Chih Liu4I-Chun Chen5Sue-Wei Lee6Yu Hsu7Dar-Ming Lai8Horng-Huei Liou9Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10051, TaiwanDepartment of Pharmacology, College of Medicine, National Taiwan University, Taipei 10051, TaiwanDepartment of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10051, TaiwanDepartment of General Internal Medicine, Taipei Medical University Hospital, College of Medicine, Taipei Medical University, Taipei 11042, TaiwanDepartment of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10051, TaiwanDepartment of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10051, TaiwanDepartment of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10051, TaiwanDepartment of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10051, TaiwanDepartment of Surgery, Division of Neurosurgery, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10051, TaiwanDepartment of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10051, TaiwanSDF-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.http://dx.doi.org/10.1155/2017/2493752
spellingShingle Shih-Yin Ho
Thai-Yen Ling
Hsing-Yu Lin
Jeffrey Tsai-Jui Liou
Fei-Chih Liu
I-Chun Chen
Sue-Wei Lee
Yu Hsu
Dar-Ming Lai
Horng-Huei Liou
SDF-1/CXCR4 Signaling Maintains Stemness Signature in Mouse Neural Stem/Progenitor Cells
Stem Cells International
title SDF-1/CXCR4 Signaling Maintains Stemness Signature in Mouse Neural Stem/Progenitor Cells
title_full SDF-1/CXCR4 Signaling Maintains Stemness Signature in Mouse Neural Stem/Progenitor Cells
title_fullStr SDF-1/CXCR4 Signaling Maintains Stemness Signature in Mouse Neural Stem/Progenitor Cells
title_full_unstemmed SDF-1/CXCR4 Signaling Maintains Stemness Signature in Mouse Neural Stem/Progenitor Cells
title_short SDF-1/CXCR4 Signaling Maintains Stemness Signature in Mouse Neural Stem/Progenitor Cells
title_sort sdf 1 cxcr4 signaling maintains stemness signature in mouse neural stem progenitor cells
url http://dx.doi.org/10.1155/2017/2493752
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