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

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

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number2493752
JournalStem Cells International
Volume2017
DOIs
Publication statusPublished - Jan 1 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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