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Original Research: Tissue-Specific Stem Cells
Article first published online: 14 FEB 2012
Copyright © 2011 AlphaMed Press
Volume 30, Issue 3, pages 510–524, March 2012
How to Cite
Zhang, Y., Liu, J., Yao, S., Li, F., Xin, L., Lai, M., Bracchi-Ricard, V., Xu, H., Yen, W., Meng, W., Liu, S., Yang, L., Karmally, S., Liu, J., Zhu, H., Gordon, J., Khalili, K., Srinivasan, S., Bethea, J. R., Mo, X. and Hu, W. (2012), Nuclear Factor Kappa B Signaling Initiates Early Differentiation of Neural Stem Cells. STEM CELLS, 30: 510–524. doi: 10.1002/stem.1006
Author contributions: Y.Z. and J.L.: performance of experiments and data analysis. S.Y., F.L, W.Y., and S.K.: animal breeding and technical assistance; L.X., M.L., H.X., W.M., S.L., L.Y., J.L., and H.Z.: collection and assembly of data; V.B. and J.G.: data analysis and interpretation and manuscript editing; K.K., S.S., and J.R.B.: provision of materials and concept and design; X.M. and W.H.: conception and design, financial support, data analysis and interpretation, manuscript writing, performance of experiments, and final approval of manuscript. Y.Z., J.L., X.M., and W.H. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS December 1, 2011.
- Issue published online: 14 FEB 2012
- Article first published online: 14 FEB 2012
- Accepted manuscript online: 1 DEC 2011 11:31AM EST
- Manuscript Accepted: 19 NOV 2011
- Manuscript Received: 20 APR 2011
- National Basic Research Program of China. Grant Number: 2007CB947802
- Nature Science Foundation of China. Grant Numbers: 30771228, 30771227
- National Institutes of Diabetes, and Kidney and Digestive Diseases. Grant Numbers: DK075964, DK080684
- Neural stem cells;
- Nuclear factor kappa B;
- Glial fibrillary acidic protein;
- Cell division
Inflammatory mediators, many of which activate the signaling of nuclear factor kappa B (NFκB), have received increasing attention in the field of neurogenesis. NFκB signaling regulates neurite outgrowth and neural plasticity as well as the proliferation/apoptosis and terminal differentiation of neural stem cells (NSCs). Early neurogenesis from NSCs produces identical progeny through symmetric division and committed daughter cells through asymmetric division. Here, we show that NFκB signaling is required for NSC initial differentiation. The canonical IKKβ/IκBα/p65 pathway is activated during the initial stages of neural differentiation induced by treatment with TNFα or withdrawal of epidermal growth factor/basic fibroblast growth factor. NSC-specific inhibition of NFκB in transgenic mice causes an accumulation of Nestin+/Sox2+/glial fibrillary acidic protein+ NSCs. Inhibition of NFκB signaling in vitro blocks differentiation and asymmetric division and maintains NSCs in an undifferentiated state. The induction of initial differentiation and asymmetry by NFκB signaling occurs through the inhibition of C/EBPβ expression. Our data reveal a novel function of NFκB signaling in early neurogenesis and provide insight into the molecular mechanisms underlying neurodevelopmental disorders and neurodegenerative diseases. STEM CELLS 2012;30:510–524